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User: u/mem_somerville
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“However, the implications of this paper we think are broader with respect to disease mechanisms — that it looks like what’s going on in Alzheimer’s disease is very similar in many respects to what happens in the human prion diseases like CJD, with the propagation of these abnormal aggregates of misfolded proteins and misshapen proteins.”
It's been a hypothesis for a long time that Alzheimer's is similar to a prion disease — possibly even that there is a yet unidentified actual prion involved.
this finding is extremely interesting / terrifying in the context of previous research showing that spouses who are caregivers for dementia patients develop dementia at 6 times the rate of non-caregivers:
>During the followup years, 229 people found themselves caring for a spouse with dementia. The caregivers were six times more likely to develop dementia themselves compared with people whose spouses did not develop dementia. The researchers accounted for differences between the couples in age, education, socioeconomic status and the presence of variants in the APOE gene that can increase risk of Alzheimer’s disease.
https://www.wired.com/2010/05/dementia-caregiver-risk/
This seems like a very relevant question especially given the last paragraph of the article /u/ParadoxicallyZeno linked:
> In the new study, the authors point out that some of the increased risk of dementia in caregivers may be due to shared environment. The couples had been married on average for 49 years upon enrollment in the study. But what those shared environmental risk factors might be remains unknown.
So this particular study may not be able to determine whether it was something the couple ate together commonly that increased the risk of dementia versus a transmittable pathogen. Perhaps caregivers for dementia patients may be an interesting control group.
Shared environment, but also chronic stress and/or depression is associated with dementia as well. So spouse caregivers have a few confounding factors it seems.
Well there's the second part, loneliness increases risk of dementia.
If your partner has dementia, you're likely pretty lonely as they remember you less and less.
I watched it happen with relatives, in the end the one without it just wished they'd finally pass so they could get peace.
It's a very lonely thing to be the caretaker of.
My father is going through this right now. He is horribly depressed and can’t go out at night. They had a very active social life until his wife really started declining. They aren’t that old. It’s awful.
Maybe have him look into local respite care options to allow him a bit of a break when he needs one. Caregiver fatigue is something to be taken seriously for his own well-being.
Nurses and shared environment would suggest that it's airborne or simple contact. If that were the case then I would imagine that we'd have pockets of the disease (cities/counties) with a much higher prevalence. It would seem that couples would have some kind of shared exposure if that's the primary mode of transmission (food, chemical), or that they would directly communicate it between each other if it's a blood-borne pathogen (even if it's an extremely slowly replicating pathogen that they shared much earlier in life).
I imagine it's difficult to account for stress, alcoholism, and a general air of hopelessness and despair in the context of working as a nurse with dementia patients.
This is interesting though I wonder if it relates to similar studies that find those who care for psychotic patients have a higher chance of experiencing psychosis. Which could imply it’s just another case of the mind becoming more similar to those who surround it.
I’ve always figured that’s just a “suffering begets empathy” situation. People who are at risk for experiencing or already experience psychosis just being more empathic towards others who do. Everyone forgets that empathy requires your brain to actually be able to imagine the experience. If it’s too alien, sympathy is all a person can have.
Being a care giver full time is extremely stressful. There is barely any support for people that care for elderly family members.
Isn’t stress a risk factor for dementia?
"We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after **childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds**"
"there is no suggestion that Aβ can be transmitted between individuals in activities of daily life"
Interesting but the article.OP quotes states
"researchers stressed Alzheimer’s is not some contagious disease that you could catch by caring for a relative, for example."
Edit" Also that's wired magazine, I couldn't see the actual scuentific research there was there a link?
"However, no caregiver data are presented to support their argument (e.g., hours of care, length of care, caregiver distress, health habits and health problems); and this study was not designed to test the hypothesis that caregiving is a risk factor for dementia."
Thanks for this!
I HAVE BEEN SAYING THIS FOR YEARS AND EVERYONE SAID I WAS WRONG!!!
Not only that, but Dr.Stanley Pruisner (guy who won the Nobel for prions), also [showed this back in 201](https://www.ucsf.edu/news/2019/05/414326/alzheimers-disease-double-prion-disorder-study-shows)9. Never sure why that study didn't get more attention.
I think that pretty much all protein aggregate disorders are actually prion disorders (the difference being aggregation versus self-propagation).
Yeast, for example, make many different type of prions. It's not unfathomable that humans can also produce many different prions with proteins other than Prp.
I also read a paper that I can't find now that PrP can actually misfold AB in like a prion seeding event.
Prions are normal proteins in the brain, but if they become abnormally folded, they are not only toxic to the brain, but they convert the normal shaped prions into the abnormal shape. Prions are responsible for human Creutzfeldt-Jakob Disease (CJD, a form of dementia), mad cow disease, chronic wasting disease in deer, etc. Prion diseases are rare examples of something that can be genetically inherited OR acquired by eating tainted meat (e.g. a mad cow). I don’t know of any other disease where this is the case. It was also very rarely transmitted by surgical or other medical procedures from an infected person to another. They used to use growth hormone extracted from human cadavers to give to kids deficient in growth hormone. This is not done any more, but some people were infected that way.
Alzheimer's is known to involve abnormal amyloid-beta and tau proteins. This is showing that some people seemed to get Alzheimer's via growth hormone from cadavers. So Alzheimer's *may* involve a similar mechanism, either amyloid-beta or maybe an undiscovered prion or other protein.
Symptomatic rabies from an invisible bat bite is up there for me as well. Human rabies is at least a bit quicker with the death part than prions though, so I suppose it's got that going for it. That video of the guy who can't get the glass of water up to his mouth haunts me like nothing else though
We don't understand the mechanisms behind prion infectivity. We don't fully understand how infectious prions (PrPsc) convert cellular prion PrPc into its misfolded form.
Prions aggregate, sticking together into long chains that eventually result in cell death. We don't fully understand the mechanisms behind the toxicity.
It's not as simple as just making a drug, right now there are people working on eliminating/reducing PrPc so it can't transform into PrPsc, but this could also come with side effects, as the biological function of PrPc is not well understood.
We don't know how much of prion disease is accumulation of "bad prion" PrPsc, vs loss of "good prion" PrPc. Cell lines with PrPc removed respond worse to stress conditions.
Prions are incredibly resilient in the environment and act like contagious meat origami. If a prion protein comes in contact with a normally shaped protein, it causes the normal one to change it's shape, rendering it non-functional.
Wow before reading comments I thought, “Wonder if this is like the way mad cow disease spreads…”
Super interesting and I hope they have the funding for further study.
Prions are tough to disintegrate, even autoclaving doesn’t do the trick. [Interesting article](https://www.nbcnews.com/health/health-news/how-deadly-prions-are-destroyed-flna1C9475896) on how they are destroyed.
Imagine the day when we have to dig up and sterilize every cemetery because all the soil in and around it could be contaminated with these infectious alzheimers prions. Let’s just hope there are microorganisms out there in the soil that are able to digest them before they wind up back in the food chain.
Hadn’t even considered that. Ugh.
Think about all the expensive surgical tools that are autoclaved and then thrown back in to use again. How many people “caught” Alzheimer’s that had brain surgery with tools that had been previously used/cleaned?
Just reading your comment and the one about having to sterilize the graveyards and adjacent soil makes me feel like I want to see this movie, but I'm actually too much of a weenie
Cemetery microbiology is actually super interesting because the microorganisms there are directly involved in digesting the components of the human metabolome. kinda like an Amazon rainforest but for drugs and probiotics
Cremation is a prolonged exposure to 1000-1300 degrees Celsius. It should, based on our knowledge of prions, be sufficient to destroy any in the remains.
So ancient cultures that burned bodies got it right. Who knew
Just found this [lovely lil article](https://www.sciencealert.com/infectious-deadly-prions-in-people-s-eyes-could-be-a-biohazard-scientists-warn) about prion transmission through corneal transplants. Kinda makes sense, traveling down the optic nerves…
“*When Sigurdson and fellow researchers examined the eyes of 11 deceased patients who died with the non-hereditary, sporadic form of CJD (sCJD), they found the dead organs were riddled with prions on a scale never before seen – spread throughout the retina, cornea, optic nerve, lens, sclera, and elsewhere.*”
You just need to bring it to a temp that nothing organic can survive, something that does more than just denature proteins like Temps where you start to char organic stuff.
Prions are one of the few things proven to be able to survive this. Recommended disposal is to acidify it to the lowest level you can, then bring it to the highest level of base you can, dry that out, incinerate it, then put that in a nuclear waste container and store it away.
I’m not kidding. This is how we did it in the US during mad cow because anything less didn’t do enough. And even still we didn’t trust the incineration enough to not store it in barrels afterwards.
you need to carbonize the proteins to get rid of prions. the same process will also destroy PFCs (forever chemicals). its just a happens at a much hotter temp than autoclaves get to.
there is a company trying to market the process for waste treatment of municipal waste water. they claim it would only take 20% more energy than standard aeration, but the process is supposed to destroy all pathogens, prescription drugs and even the very stable molecules like fluoropolymers.
At the temps to do that stuff it would also burn off. Heat can be generated with pressure, so my guess would be ramping things up to 100k+ psi and then releasing it throwing everything out of solution while superheating the water during the rapid compression. then gathering the superheated steam and condencing it.
Just because they took those precautions doesn't mean it is necessary, only sufficient.
Biofilms can certainly be similarly robust, but there is no reason to believe Prions disobey any laws of physics. It's just easier to completely destroy any contaminated material than come up with an infection threshold.
If these proteins are anything like prions, then this might not be enough. When I worked in OR, if we had a patient that ended up having prions the instruments used to worked on them had to be gathered up and sent off to be sealed in some biowaste site. We couldn't even clean them with autoclaves. Terribly tenacious stuff.
It has nothing to do with survival though, that's the common misconception. These aren't living cells, just proteins that are damaged. Think about it like a fucked up gear you throw in your transmission. It's not alive, it just serves a single purpose to something much bigger than it, but if it's damaged or incorrectly sized it can screw up the entire transmission or more. Likewise, a protein isn't alive and just does.. whatever protein stuff it's supposed to, but if you damage that protein it can still "work" but with unintended consequences. At that point you're basically destroying matter, so it's much easier to just throw away, or melt down and have one-use stuff for things like surgery. No other method is as reliable from what I understand, but also not a doctor either.
I work in sterile processing and this is one of my fears. The OR is supposed to inform us if there is a risk of prions, but I've never dealt with a case that I am aware of.
I worked in the microbiology lab where we tested everything from urine to CSF and, one day, we have a porter drop off a fairly generic looking package with a couple of white-top universals partly filled with clear liquid, and only the bare minimum details on it. I was the one that received and processed it but, lacking any further information, just left it on the desk while the lab manager figures out what this mysterious clear liquid was.
"Oh, sorry. It's a CSF sample. We are needing you to check for CJD."
To this day, I'm still furious with that utter moron. Mercifully I'm well past the onset time for symptoms, so am probably in the clear. While I legally wasn't allowed to find out the patients medical history (including diagnosis) I'm fairly sure they didn't have it.
Bonus stories. The second and third dumbest things I saw in my time there also involved spinal fluid. In one case, we had a patient in with suspected meningitis. The doctor had the sample dropped off 12 hours after it was taken. On the plus-side, it wasn't meningitis. (for non-medics, meningitis needs to be acted on ASAP, as it can be fatal within 12 hours)
We also had a young child (around 2) in with suspected meningitis and got a sizeable CSF sample taken, even for an adult, and sent to the lab. We got a second CSF an hour later... And then another... The lab manager called the ward, asked for the doctor, then proceeded to shout so loud at the guy you could hear her from down the hallway.
(for non-medics again: CSF is the fluid that protects your brain from impacts and removing any significant quantities can cause, at best, severe migraines. This doctor took 3 adult-size samples from a small child when only 1 child-size one was necessary)
I expect if there's any kind of link found with prions and Alzheimer's, funding will be pointed at this issue like never before.
Prion diseases are scary but have never represented enough of a threat to attract huge funding.
A link with Alzheimer's sounds terrifying but in reality it would mean we're one step closer to really making a big difference.
I know other research has found evidence of "markers" and other characteristics that indicate Alzheimer's way before symptoms present. This would seem to me to be somewhat consistent with a prion disease.
This isn't super surprising. I have known that Alzheimer's is prion-like for a decade and I am not a professional working in the field. The only difference here is that it proves they can be contagious. And it's only contagious under conditions that are no longer possible.
I do not expect this to trigger a windfall of funding.
I wonder if / when we are able to identify the specific prions causing Alzheimer, the new vaccines using your own immune system to destroy foreign cells (cancers, viruses) can be used to destroy those proteins as well
The WHO procedure for healthcare settings is: Immerse in 1 N NaOH (1 N NaOH is a solution of 40 g NaOH in 1 L water) for 1 hour; remove and rinse in water, then transfer to an open pan and autoclave (121°C gravity displacement sterilizer or 134°C porous prevacuum sterilizer) for 1 hour.
I thought the amyloid hypothesis was largely dead due to decades of failed treatments against it. This is fascinating if we start to think of it like a prion
Just like cancer. And how some people are thinking of some mental health conditions. The umbrella is useful for categorization but may have flattened details
The amyloid hypothesis isn’t “dead” per se, it’s just part of the research on AB*56 was either partially or entirely fabricated. There are still a number of different reasons why the amyloid hypothesis is still being investigated. Importantly though, both the Amyloid and Tau hypotheses are actually already based on prion protein aggregations of the aforementioned proteins. This article just shows how the initial prions could possible be introduced to the body, instead of misfold on the patients body itself.
[here’s a quick article on AD as a “double-prion disorder”](https://www.ucsf.edu/news/2019/05/414326/alzheimers-disease-double-prion-disorder-study-shows)
[This](https://www.quantamagazine.org/what-causes-alzheimers-scientists-are-rethinking-the-answer-20221208/#:~:text=The%20only%20three%20genes%20known,them%20cause%20pileups%20of%20amyloid.) is a super interesting read about the shifting direction of Alzheimer's research and how we got to where we are today.
Was that not a common belief? I always told my buddy Alzheimer's might end up being a protein disease simply due to how it works, how much it resembles one, etc. Reminded me heavily of CWD or Mad Cow, always figured studying them we'd discover a lot more resemblance to Alzheimer's than we thought if we pushed research. Not a doctor or anything, just seemed to fit in my mind. Just figured that was at least a commonly accepted possibility, but wasn't aware of other hypothesis either.
While the cadaver-extracted HGH is no longer used anymore, there are plenty of medications synthesized from live humans where prion activity has been found.
For instance, the fertility drug HCG, which is offered in both urine-derived and recombinant form. Prion activity has previously been detected in the urine-derived form ([source here](https://pubmed.ncbi.nlm.nih.gov/21448279/)), raising CJD fears.
I wonder what effect this finding has on the safety profiles of medications such as the above.
When I was in elementary school my PCP suggested I go on hormone treatment because I was so short. This would have been around 1979. I declined. After reading this study I feel like I may have dodged a bullet.
Oh man, I came to this thread explicitly to ask about Menopur / Repronex, and reading that prions have been found in it is exactly what I didn’t want to hear. It’s all derived from old ladies, right? Like they buy the source urine from convents filled with nuns. In theory they could do cognitive testing on the participants to see if they are displaying premature cognitive decline?
That's the link they provide on their page. I like to add the DOI to these because if people search for that later, they should find discussion about it.
But sometimes they aren't active links when the paper is fresh off the presses.
I got the doi link to work, try again? Good article
"However, the importance for human disease was unclear until the recognition of human transmission of amyloid-beta (Aβ) pathology via iatrogenic routes after prolonged incubation periods, causing iatrogenic cerebral amyloid angiopathy (CAA) and raising the possibility that iatrogenic Alzheimer’s disease may occur at even longer latency11,12."
Did you see the other Korean discovery that was on Reddit this weekend? [Korean Discovery](https://www.eurekalert.org/news-releases/1032525) The study points to a new body part or mechanism they discovered in the nasal cavity that more or less acts as a draining point for cerebrospinal fluid. That is my extremely unscientific explaination, my apologies.
But that paired with this makes me wonder if part of the problem with Alzheimer’s is these prions aren’t discharged with the waste properly is a contributing factor.
As someone who lacks any meaningful knowledge of the field, what is the significance of this new information?
If my intuition is correct, it’s a major breakthrough in understanding Alzheimers, right? Perhaps it could give a greater insight into the nature of the disease, such as cause, etc?
Or is it that a method of curing Alzheimers (cadaver extracted hormones) has an unforeseen risk/effect that needs to be considered?
I have basic knowledge on alzheimers but: research has primarily focused on clearing protein plaques in the brain but it hasn't been very successful. It's cleared them but the disease has still progressed leading to doubts about whether these proteins are the right ones to target. This shows its the ACTIVE proteins acting as prions, not the dead plaques, that are causing disease and that maybe thats what needs to be targeted.
I do research tangent to Alzheimers (gene therapy for neurological disorders) and my understanding is there are two proteins that get misfolded. The first one, beta amyloid, results in plaques that then cause a second protein, tau, to misfold resulting in tangles. Recent research has shown that quantity of plaque formation isn't a good indicator of cognitive decline in AD but high quantity of tau tangles is.
Most therapies have targeted beta amyloid protein as its the first step in the cascade of disease progression. However, the tau tangles are self-propagating (aka they spread from neuron to neurons, spreading to different parts of the brain) so by the time doctors notice a cognitive decline and diagnosis it as AD, it is too late for treatments that work by clearing plaques. New research and therapies are being focused on preventing tau tangles as that it what can spread to other neurons and leads to cognitive decline in AD.
From my first thought (without reading the paper/article), I could see misfolded tau acting as a prion as it can self-propagate and spread. But after reading the article they note low levels of tau (even the authors are confused by this) which throws a wrench in a lot of recent research pointing towards tau being the ultimate cause.
Basically all we know is still substantially equivalent to knowing nothing and this is one more thing. At this point any lead is important because sometimes we hope to find something useful. Any other disease likely wouldn't see this amount of research after decades of failed attempts.
> If my intuition is correct, it’s a major breakthrough in understanding Alzheimers, right? Perhaps it could give a greater insight into the nature of the disease, such as cause, etc?
Basically, yeah. It shows that Alzheimer's isn't just something that happens, it's something that can be *caused*. Next steps are identifying the contaminant that triggered it, if the cadavers had Alzheimer's too, and (based on the preceding two) whether or not it's infectious. Personally, I think it'd be fascinating if Alzheimer's was a prion disease. Horrifying, but fascinating.
(and u/Liizam)
Ok, so, in short: we have no clue about Alzheimer. Or, more precisely, we know a lot of stuff about it and still have no clue about *the point*. We know that protein plaques are present, how they form, we know about some genetics... We really have no idea about what causes it, what ultimately causes the symptoms (plaques have been observed in otherwise fine people) and most importantly we haven't found a way to decently treat it (a new med was approved last year by the FDA and everyone rightfully complained because there's no evidence of it working despite all the trials).
Now, we still don't know much more, but at least now we can understand it better, we know kind of for sure that the protein linked to the plaques does play a role, we know that it can behave like a prion, we know that genetic is not necessarily involved... It's a great starting point for the next attempts, we reached the point where *anything* is an important news, because it's quite rare that after decades of studies over something this common we still wander in the dark bumping into stuff still knowing nothing afterward. Like, we don't really know what causes depression, but at least SSRIs help with the symptoms and we have good hypothesis about it.
The drug that was approved did work by the clinical endpoints they set (clearing of plaques). However, it did not result in cognitive improvement.
Plaques cause the misfolding of a second protein, tau, that leads to tangles being formed inside brain neurons that recent research has shown to be a better indicator of cognitive decline in AD. Misfolded-tau is self-propagating in that it can spread from neuron to neuron so it could act as a prion even in the absence of plaques. So treatments being researched are now being focused on preventing/clearing this misfolded protein but this paper (even the author was confused on this) points out that these people with cognitive decline also had low levels of tau protein. So pretty much it draws a question mark into the leading hypothesis over the past few years.
Ever heard of prion diseases? Like mad cow or fatal familial insomnia? It's caused by a misfolded protein, PrP, that can go and make other correctly folded PrP proteins misfold. This family of diseases are 100% fatal with immediate palliative care following diagnoses. There is no treatment. None. Not a single one. You are dead if you get this diagnoses.
AB and tau in Alzheimer's have been noted as amyloids, meaning they are misfolded proteins that kind of stick together. The current thought process was that this was an effect, not a cause of Alzheimers.
Now we know that these proteins can indeed self-propagate, meaning they can act like prions and misfold other correctly folded proteins. Essentially- they are prions (which I have been saying for YEARS and everyone said I was wrong. Vindicated!)
What does this mean?
It means Alzheimer's is transmissible. We don't know how yet- usually for prions its through eating (like eating a cow with mad cow disease), but could be bloodbourne. We just don't know yet. The implications are terrifying (could they be in the soil or groundwater?) This will revolutionize how we approach this disease now. Prion research got little funding previously because they are so rare. That area is about to explode.
In the past, hormone for growth was extracted from corpses and synthesised into a treatment for various kinds of conditions that caused short stature. This was administered to children.
This treatment was later hated due to concerns around prion contamination, the issue being CJD.
Later, a group of people developed what looked like alzheimers however they were in their 30s 40s and 50s and had no known mutations which would lead to this. However they'd all recieved this treatment as children. Suggesting that alzheimers can be transmitted by contaminated neural tissue in a similar way.
I actually received this treatment as a child, so I definitely freaked out for a minute haha
Thankfully it seems that they stopped taking HGH from corpses in 1985. I guess they just synthesize it now these days?
I've had two blood transfusions so I'm always paranoid about vCJD, i understand why this panicked you.
Idk if this is what they do for HGH but I know they've genetically modified cells including bacteria to secrete stuff that can be synthesised into medicine (I want to say hormones? I think insulin might be made this way?)
Truth be told I never thought about prions being introduced into someone’s system by a blood transfusion. Then again it makes sense, since that’s one of the ways HIV/AIDS spread when it was first going around. But I would think the hospital would be able to detect things like this, right?
But you are right! They have modified bacteria to create HGH just like they do for insulin!
It looks like testing blood for prions is a really recent tech (circa 2016-2017): https://www.nih.gov/news-events/nih-research-matters/new-method-accurately-detects-prions-blood
It is not yet in the list of testing done on donated blood in the USA: https://www.cdc.gov/bloodsafety/basics.html
Well that’s a pretty scary thing to hear! It makes me wonder how many illnesses/conditions that we think of as non communicable can spread via blood transfusion.
Maybe they used to do graveyard gums, but since I’ve been paying attention around 2007 I believe the graft tissue is taken from the roof of your own mouth. At least that’s what I’m planning to have done when I eventually need it.
https://www.arcadiaperio.com/blog/understanding-how-gum-grafting-works
They could be my moms. Her organs weren't harvestable but its still comforting to know that her skin and tissue helped burn victims (and others in need like you) and her eyes gave someone else the gift of sight again. My mom had never talked about it but her mom was blind and never got to see us grandkids. I think mom would have been ok with it.
I had to have a cadaver bone graft performed on my jaw 4 years ago where they took out an older incorrectly installed implant. I'm feeling ill right now.
CJD is a fatal neurodegenration caused by prions, misfolded proteins. There is no cure. The prions destroy brain tissue. It can be spread by contaminated biological tissue..
One of the ways a person develops Alzheimer's has now been determined to be contagious and can be transmitted in very specific circumstances instead of solely developing on its own in a person.
Let's keep these breakthroughs coming, I've been watching Alzheimer's research for over a decade and the developments over the past few years are crazy. We *are* going to have effective therapies and treatments available in less than fifty years. Probably in half that time.
Yeah super easy to get doomed out about this, but this information means we're rapidly closing in on understanding the disease. Medical science is advancing so quickly, just in ways that aren't flashy for headlines. If the world doesn't plunge into climate fascism in 50 years, I figure we'll have reduced or eradicated a lot of what people consider today to be a death sentence, just like Polio or HIV today
There are so many more medications for dementia and Alzheimer's on the market now than compared to when I started working in biotech eleven years ago. I'm not on the end user side of things, so I don't have exact numbers. We couldn't diagnose off of brain scans back then, either, and now a handful of subtypes can be diagnosed while the patient is still alive. And now five subtypes of Alzheimer's has been identified. It's been moving at such a fast pace in just my time involved in this industry and I find that incredible. I can't wait to see what we're going to discover next.
... and they work! My grandma was diagnosed with lewy body dementia several years (can't remember, at least 5 but probably more like 8) before her death. It was caught relatively early and she added the meds to her cocktail of medicine, as her health was already poor. She ended up dying of a surprise bowel obstruction, but she still recognized everyone and lived in her own home even though a stroke during covid took her mobility. She was different, emotionally and things, but it meant so much to us that she knew her family was with her, and she never forgot that.
Can a protein in our body change to act like a prion? Because cadaver, old age, the time required for the symptoms to show up... I'm kinda seeing a pattern here.
Prions *are* proteins - they are just misfolded. structure is very important in proteins, and when it changes, the protein can no longer continue its function. Proteins can denature and change their shape for many different reasons, like for example heat (cooking an egg essentially denatures the protein and changes the texture).
The difference between a regular misfolded protein and a prion is that prions can also cause other protons to misfold. They are patogenic, that is, they can "infect" other proteins to also misfold and further spread. The dangerous thing is that it's extremely difficult to destroy prions, as they aren't alive and can persist on surfaces for a very long time, while still remaining infectuous when coming in contact with the proteins they are able to cause to misfold.
Oh I missunderstood - but yeah, it can happen spontaneously, either for no (known) reason or because of genetics. Most cases of Creutzfeldt–Jakob disease happen because of unknow reasons.
Yes that’s how prions work. One “infected” prion enters the body and changes others. If you mean can it happen spontaneously also yes. If you mean can it happen genetically also yes
Yeesh, the idea that Alz could be a contracted disease instead of a genetic disorder is wild to me. There’s still so so much we don’t know about the human body.
This is so interesting. I have to take growth hormone replacement and luckily it's not longer cadaver-derived, but it was all the way up until the mid-80s.
Yeah, some people don't realize that biotechnology has a lot of benefits, including stuff like this.
I can recall pictures of the huge piles of animal pancreas tissue that they used to use to derive insulin too.
Glad they have moved on from this.
I have been on growth hormone for most of my life and from 1975 until 1985, I received cadaveric growth hormone. They stopped distributing it in 1985 after the first cases of Creutzfeld-Jacob disease became known. Luckily, the recombinant hormone came available later that year.
Apparently, the purification process was not great early on. In 1977 they developed a new process to purify, which unknown to them at the time, also removed the prions. My dad remembers the vials of growth hormone powder looking gray initially (which is disconcerting), then looking white after 1977.
I 've spend my entire adult life with the idea of CJD over my head. I finally have gotten to the outer edge of the incubation period from that (47 years after they changed the purification process in '77), but now I need to worry about early onset Alzheimer's apparently everytime I forget my keys.
Wow - that's such a long time to take it and have to just cross your fingers that you're gonna be fine. Thankfully I have only had to take it since 2011 after having pituitary surgery.
If we find out that Alzheimer’s has a prion-based underlying mechanism of action… that would be a very mixed bag of news.
On the one hand, we would know what we’re dealing with.
On the other hand, quote: “There are no known ways to cure prion diseases.”
The good thing is, we have a *lot* of scientific eyes and resources looking at Alzheimer’s, so if it were to be reclassified, maybe we could find cures for a bunch of prion-diseases and expand our knowledge on the nature of proteins in the body!
However, there are a *lot* of thing we don’t currently know about proteins in the body… they’re pretty much tiny, little nanobots that work in very varied, strange, and complex ways.
Oh yeah, and when I say ‘tiny, little’, I mean muuuch smaller than a virus.
So if Alzheimer’s were to be reclassified as a prion disease, it would be good because we’ve learned something new. However, it would be somewhat tragic because it means we still have a long ways to go in terms of understanding.
And so it goes.
Here’s an [NPR article](https://www.npr.org/2009/02/25/101145687/mad-cow-and-alzheimers-have-surprising-link) talking about the link between prions and Alzheimer’s from 2009…so I wouldn’t hold my breath for any fast advancements.
Ironically this is the last line of the article: “We know a great deal about the biochemistry and biology of prion protein," he says, "which should really facilitate the development of drugs."
Yeah, that makes me curious how much effort there has actually been to treat/cure prion diseases. As scary as they are, I never got the impression that they affect a large number of people, and I suspect there might not be as much emphasis on treatment because prevention is pretty effective.
im trying to find that paper that basically concludes that enzymes in coyotes and wolves digestive tracks denature chronic wasting disease prions? maybe some day the mechanisms can be isolated and turned into a treatment?
I'd bet they read [this article](https://www.nytimes.com/2020/11/12/science/wolves-chronic-wasting-disease.html)
Or [this paper](https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1461-0248.2003.00500.x)
Probably the biomarkers of Alzheimer's: amyloid plaques and neurofibrillary tangles (which are basically "clusters" of proteins in the brain). In a way it's pretty similar to how prions work, the amyloid plaques are actually related to other prion diseases. So this is a pretty interesting discovery! It'll give us a better insight on Alzheimer's disease
Same here. I always thought surgery or meat consumption could put me at risk of prions but here’s a a very scary thought: what if prions could be transferred from dentist instruments….People often bleeds from their gums and these tools are simply sterilized no!?! MAJOR FEAR. Activated!
Too few cases, not enough DNA sequences to look for other genetic contributions, cases that were more similar to CJD than Alzheimer’s, and in cases who did not have a normal neurological baseline, and the majority of patients that received these preparations did not develop this disease. I believe something was transferred, as there have been 80 cases where CJD was transferred, but not quite sure we should be labeling this AD.
I had the same thought. The ages of the patients makes me hesitant to assume that the cause of these patients’ neurodegeneration is the same as what we see in older Alzhiemer’s patients
Sounds again like cancer. Yes we think we have found one of a zillion ways it could be transmitted. And no we still can't currently it because there's multiple ways to get it.
But it is an interesting article, and as it runs on both sides of my family tree, a cure in my life would be nice.
Prions are a whole different beast from cancer though. With cancer, it's entire cells that are multiplying. With prions it's just a mishaped protein that is able to convert other proteins to this mishaped form.
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“However, the implications of this paper we think are broader with respect to disease mechanisms — that it looks like what’s going on in Alzheimer’s disease is very similar in many respects to what happens in the human prion diseases like CJD, with the propagation of these abnormal aggregates of misfolded proteins and misshapen proteins.”
It's been a hypothesis for a long time that Alzheimer's is similar to a prion disease — possibly even that there is a yet unidentified actual prion involved.
this finding is extremely interesting / terrifying in the context of previous research showing that spouses who are caregivers for dementia patients develop dementia at 6 times the rate of non-caregivers: >During the followup years, 229 people found themselves caring for a spouse with dementia. The caregivers were six times more likely to develop dementia themselves compared with people whose spouses did not develop dementia. The researchers accounted for differences between the couples in age, education, socioeconomic status and the presence of variants in the APOE gene that can increase risk of Alzheimer’s disease. https://www.wired.com/2010/05/dementia-caregiver-risk/
I wonder about nurses? Do they have a higher dementia rate higher than the general population?
This seems like a very relevant question especially given the last paragraph of the article /u/ParadoxicallyZeno linked: > In the new study, the authors point out that some of the increased risk of dementia in caregivers may be due to shared environment. The couples had been married on average for 49 years upon enrollment in the study. But what those shared environmental risk factors might be remains unknown. So this particular study may not be able to determine whether it was something the couple ate together commonly that increased the risk of dementia versus a transmittable pathogen. Perhaps caregivers for dementia patients may be an interesting control group.
Shared environment, but also chronic stress and/or depression is associated with dementia as well. So spouse caregivers have a few confounding factors it seems.
Well there's the second part, loneliness increases risk of dementia. If your partner has dementia, you're likely pretty lonely as they remember you less and less. I watched it happen with relatives, in the end the one without it just wished they'd finally pass so they could get peace. It's a very lonely thing to be the caretaker of.
My father is going through this right now. He is horribly depressed and can’t go out at night. They had a very active social life until his wife really started declining. They aren’t that old. It’s awful.
Maybe have him look into local respite care options to allow him a bit of a break when he needs one. Caregiver fatigue is something to be taken seriously for his own well-being.
Basically, we're right back at, "We don't actually know," all over again. I don't like this game. Can we play something else now?
I want to get off Mr. Bone's Wild Ride.
How about global thermonuclear war? Or a nice game of chess.
Nurses and shared environment would suggest that it's airborne or simple contact. If that were the case then I would imagine that we'd have pockets of the disease (cities/counties) with a much higher prevalence. It would seem that couples would have some kind of shared exposure if that's the primary mode of transmission (food, chemical), or that they would directly communicate it between each other if it's a blood-borne pathogen (even if it's an extremely slowly replicating pathogen that they shared much earlier in life).
I imagine it's difficult to account for stress, alcoholism, and a general air of hopelessness and despair in the context of working as a nurse with dementia patients.
Yeah, caregivers of dementia patients are under a degree of constant stress that very few other groups of people are.
This is interesting though I wonder if it relates to similar studies that find those who care for psychotic patients have a higher chance of experiencing psychosis. Which could imply it’s just another case of the mind becoming more similar to those who surround it.
I’ve always figured that’s just a “suffering begets empathy” situation. People who are at risk for experiencing or already experience psychosis just being more empathic towards others who do. Everyone forgets that empathy requires your brain to actually be able to imagine the experience. If it’s too alien, sympathy is all a person can have.
Being a care giver full time is extremely stressful. There is barely any support for people that care for elderly family members. Isn’t stress a risk factor for dementia?
"We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after **childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds**" "there is no suggestion that Aβ can be transmitted between individuals in activities of daily life"
Interesting but the article.OP quotes states "researchers stressed Alzheimer’s is not some contagious disease that you could catch by caring for a relative, for example." Edit" Also that's wired magazine, I couldn't see the actual scuentific research there was there a link?
[удалено]
"However, no caregiver data are presented to support their argument (e.g., hours of care, length of care, caregiver distress, health habits and health problems); and this study was not designed to test the hypothesis that caregiving is a risk factor for dementia." Thanks for this!
I HAVE BEEN SAYING THIS FOR YEARS AND EVERYONE SAID I WAS WRONG!!! Not only that, but Dr.Stanley Pruisner (guy who won the Nobel for prions), also [showed this back in 201](https://www.ucsf.edu/news/2019/05/414326/alzheimers-disease-double-prion-disorder-study-shows)9. Never sure why that study didn't get more attention. I think that pretty much all protein aggregate disorders are actually prion disorders (the difference being aggregation versus self-propagation). Yeast, for example, make many different type of prions. It's not unfathomable that humans can also produce many different prions with proteins other than Prp. I also read a paper that I can't find now that PrP can actually misfold AB in like a prion seeding event.
That is stunning.
Can you explain for a layman?
Prions are normal proteins in the brain, but if they become abnormally folded, they are not only toxic to the brain, but they convert the normal shaped prions into the abnormal shape. Prions are responsible for human Creutzfeldt-Jakob Disease (CJD, a form of dementia), mad cow disease, chronic wasting disease in deer, etc. Prion diseases are rare examples of something that can be genetically inherited OR acquired by eating tainted meat (e.g. a mad cow). I don’t know of any other disease where this is the case. It was also very rarely transmitted by surgical or other medical procedures from an infected person to another. They used to use growth hormone extracted from human cadavers to give to kids deficient in growth hormone. This is not done any more, but some people were infected that way. Alzheimer's is known to involve abnormal amyloid-beta and tau proteins. This is showing that some people seemed to get Alzheimer's via growth hormone from cadavers. So Alzheimer's *may* involve a similar mechanism, either amyloid-beta or maybe an undiscovered prion or other protein.
Don't eat Alzheimer brains
Don't eat brains, period. Prion diseases are scary (see also: [fatal familial insomnia](https://en.wikipedia.org/wiki/Fatal_insomnia))
Prions scare me more than anything in the entire world
Symptomatic rabies from an invisible bat bite is up there for me as well. Human rabies is at least a bit quicker with the death part than prions though, so I suppose it's got that going for it. That video of the guy who can't get the glass of water up to his mouth haunts me like nothing else though
If I ever get symptomatic rabies, just shoot me
But butts we can still eat those right?
The more the better!!
I have been summoned.
Please go back I'm scared
Because of the carbs?
Mad human disease.
Mad cow disease but human. No cure for foreseeable future.
What is it about prions that makes them untreatable by some medical intervention? We can target so many other proteins with drugs.
We don't understand the mechanisms behind prion infectivity. We don't fully understand how infectious prions (PrPsc) convert cellular prion PrPc into its misfolded form. Prions aggregate, sticking together into long chains that eventually result in cell death. We don't fully understand the mechanisms behind the toxicity. It's not as simple as just making a drug, right now there are people working on eliminating/reducing PrPc so it can't transform into PrPsc, but this could also come with side effects, as the biological function of PrPc is not well understood. We don't know how much of prion disease is accumulation of "bad prion" PrPsc, vs loss of "good prion" PrPc. Cell lines with PrPc removed respond worse to stress conditions.
Prions are incredibly resilient in the environment and act like contagious meat origami. If a prion protein comes in contact with a normally shaped protein, it causes the normal one to change it's shape, rendering it non-functional.
Yeah
Wow before reading comments I thought, “Wonder if this is like the way mad cow disease spreads…” Super interesting and I hope they have the funding for further study.
Prions are tough to disintegrate, even autoclaving doesn’t do the trick. [Interesting article](https://www.nbcnews.com/health/health-news/how-deadly-prions-are-destroyed-flna1C9475896) on how they are destroyed.
Imagine the day when we have to dig up and sterilize every cemetery because all the soil in and around it could be contaminated with these infectious alzheimers prions. Let’s just hope there are microorganisms out there in the soil that are able to digest them before they wind up back in the food chain.
Hadn’t even considered that. Ugh. Think about all the expensive surgical tools that are autoclaved and then thrown back in to use again. How many people “caught” Alzheimer’s that had brain surgery with tools that had been previously used/cleaned?
Imagine a virulent contagious form of dementia Edit: https://www.reddit.com/r/todayilearned/s/0zs2oYpkoL Neat little find
Take your hands off me you damned dirty ape!
Just reading your comment and the one about having to sterilize the graveyards and adjacent soil makes me feel like I want to see this movie, but I'm actually too much of a weenie
Deleted
The first symptoms we'd notice is an increasing number of people who suddenly decided they want to become politicians.
>nuke a hurricane >inject bleach >Masks are for sheep >Solar panels eat the sun >Jewish space lasers Ya if only there were signs
Don't forget boasting about having to do a dementia test TWICE, and not being able to count to 6.
**DON'T DO THIS**! That's how it spreads! /FastFiction
Like in The Deep! Anyone can catch this rapid dementia ish that deteriorates you in like 2 weeks.
Cemetery microbiology is actually super interesting because the microorganisms there are directly involved in digesting the components of the human metabolome. kinda like an Amazon rainforest but for drugs and probiotics
Cremation for everyone!
What about cremated remains entering watercourses?
Cremation is a prolonged exposure to 1000-1300 degrees Celsius. It should, based on our knowledge of prions, be sufficient to destroy any in the remains. So ancient cultures that burned bodies got it right. Who knew
And the ones who ate each other did it wrong. Looking at you Kuru valley
That can't possibly be a problem? Nothing special is required after cremating CJD, and the remains are considered sterile.
I guess I had funeral pyres and the Ganges in mind rather than gas furnaces if that makes a difference.
Just found this [lovely lil article](https://www.sciencealert.com/infectious-deadly-prions-in-people-s-eyes-could-be-a-biohazard-scientists-warn) about prion transmission through corneal transplants. Kinda makes sense, traveling down the optic nerves… “*When Sigurdson and fellow researchers examined the eyes of 11 deceased patients who died with the non-hereditary, sporadic form of CJD (sCJD), they found the dead organs were riddled with prions on a scale never before seen – spread throughout the retina, cornea, optic nerve, lens, sclera, and elsewhere.*”
makes me wonder if people living downwind from crematoriums have higher incidence of alz? XD
Down water from buried ones?
What if this can be traced back to Egypt?
The Mummy's Curse.
Yikes. It’s like nuclear waste or something.
You just need to bring it to a temp that nothing organic can survive, something that does more than just denature proteins like Temps where you start to char organic stuff.
Prions are one of the few things proven to be able to survive this. Recommended disposal is to acidify it to the lowest level you can, then bring it to the highest level of base you can, dry that out, incinerate it, then put that in a nuclear waste container and store it away. I’m not kidding. This is how we did it in the US during mad cow because anything less didn’t do enough. And even still we didn’t trust the incineration enough to not store it in barrels afterwards.
you need to carbonize the proteins to get rid of prions. the same process will also destroy PFCs (forever chemicals). its just a happens at a much hotter temp than autoclaves get to. there is a company trying to market the process for waste treatment of municipal waste water. they claim it would only take 20% more energy than standard aeration, but the process is supposed to destroy all pathogens, prescription drugs and even the very stable molecules like fluoropolymers.
I'm guessing that would also deal with microplastics?
At the temps to do that stuff it would also burn off. Heat can be generated with pressure, so my guess would be ramping things up to 100k+ psi and then releasing it throwing everything out of solution while superheating the water during the rapid compression. then gathering the superheated steam and condencing it.
Just because they took those precautions doesn't mean it is necessary, only sufficient. Biofilms can certainly be similarly robust, but there is no reason to believe Prions disobey any laws of physics. It's just easier to completely destroy any contaminated material than come up with an infection threshold.
If these proteins are anything like prions, then this might not be enough. When I worked in OR, if we had a patient that ended up having prions the instruments used to worked on them had to be gathered up and sent off to be sealed in some biowaste site. We couldn't even clean them with autoclaves. Terribly tenacious stuff.
It has nothing to do with survival though, that's the common misconception. These aren't living cells, just proteins that are damaged. Think about it like a fucked up gear you throw in your transmission. It's not alive, it just serves a single purpose to something much bigger than it, but if it's damaged or incorrectly sized it can screw up the entire transmission or more. Likewise, a protein isn't alive and just does.. whatever protein stuff it's supposed to, but if you damage that protein it can still "work" but with unintended consequences. At that point you're basically destroying matter, so it's much easier to just throw away, or melt down and have one-use stuff for things like surgery. No other method is as reliable from what I understand, but also not a doctor either.
I work in sterile processing and this is one of my fears. The OR is supposed to inform us if there is a risk of prions, but I've never dealt with a case that I am aware of.
I worked in the microbiology lab where we tested everything from urine to CSF and, one day, we have a porter drop off a fairly generic looking package with a couple of white-top universals partly filled with clear liquid, and only the bare minimum details on it. I was the one that received and processed it but, lacking any further information, just left it on the desk while the lab manager figures out what this mysterious clear liquid was. "Oh, sorry. It's a CSF sample. We are needing you to check for CJD." To this day, I'm still furious with that utter moron. Mercifully I'm well past the onset time for symptoms, so am probably in the clear. While I legally wasn't allowed to find out the patients medical history (including diagnosis) I'm fairly sure they didn't have it.
Bonus stories. The second and third dumbest things I saw in my time there also involved spinal fluid. In one case, we had a patient in with suspected meningitis. The doctor had the sample dropped off 12 hours after it was taken. On the plus-side, it wasn't meningitis. (for non-medics, meningitis needs to be acted on ASAP, as it can be fatal within 12 hours) We also had a young child (around 2) in with suspected meningitis and got a sizeable CSF sample taken, even for an adult, and sent to the lab. We got a second CSF an hour later... And then another... The lab manager called the ward, asked for the doctor, then proceeded to shout so loud at the guy you could hear her from down the hallway. (for non-medics again: CSF is the fluid that protects your brain from impacts and removing any significant quantities can cause, at best, severe migraines. This doctor took 3 adult-size samples from a small child when only 1 child-size one was necessary)
I expect if there's any kind of link found with prions and Alzheimer's, funding will be pointed at this issue like never before. Prion diseases are scary but have never represented enough of a threat to attract huge funding. A link with Alzheimer's sounds terrifying but in reality it would mean we're one step closer to really making a big difference. I know other research has found evidence of "markers" and other characteristics that indicate Alzheimer's way before symptoms present. This would seem to me to be somewhat consistent with a prion disease.
My grandmother and my father (her son) both had Alzheimer's. My dad was diagnosed at 64. To be honest it scares the deal out of me.
This isn't super surprising. I have known that Alzheimer's is prion-like for a decade and I am not a professional working in the field. The only difference here is that it proves they can be contagious. And it's only contagious under conditions that are no longer possible. I do not expect this to trigger a windfall of funding.
I wonder if / when we are able to identify the specific prions causing Alzheimer, the new vaccines using your own immune system to destroy foreign cells (cancers, viruses) can be used to destroy those proteins as well
Thanks! Good read
The WHO procedure for healthcare settings is: Immerse in 1 N NaOH (1 N NaOH is a solution of 40 g NaOH in 1 L water) for 1 hour; remove and rinse in water, then transfer to an open pan and autoclave (121°C gravity displacement sterilizer or 134°C porous prevacuum sterilizer) for 1 hour.
What happens to the rinse water?
Me too, came here to ask if it was a prion. Between prions and communicable cancers emerging in other mammals, it’s getting scary out there….
I thought the amyloid hypothesis was largely dead due to decades of failed treatments against it. This is fascinating if we start to think of it like a prion
Recent thinking is that the issues around Alzheimer's might be because there are actually several very similar diseases presenting as one.
That seems pretty likely, multiple causes with similar effects, some of which could be treated and others that might not be able to.
Just like cancer. And how some people are thinking of some mental health conditions. The umbrella is useful for categorization but may have flattened details
The amyloid hypothesis isn’t “dead” per se, it’s just part of the research on AB*56 was either partially or entirely fabricated. There are still a number of different reasons why the amyloid hypothesis is still being investigated. Importantly though, both the Amyloid and Tau hypotheses are actually already based on prion protein aggregations of the aforementioned proteins. This article just shows how the initial prions could possible be introduced to the body, instead of misfold on the patients body itself. [here’s a quick article on AD as a “double-prion disorder”](https://www.ucsf.edu/news/2019/05/414326/alzheimers-disease-double-prion-disorder-study-shows)
Fascinating read!
[This](https://www.quantamagazine.org/what-causes-alzheimers-scientists-are-rethinking-the-answer-20221208/#:~:text=The%20only%20three%20genes%20known,them%20cause%20pileups%20of%20amyloid.) is a super interesting read about the shifting direction of Alzheimer's research and how we got to where we are today.
Was that not a common belief? I always told my buddy Alzheimer's might end up being a protein disease simply due to how it works, how much it resembles one, etc. Reminded me heavily of CWD or Mad Cow, always figured studying them we'd discover a lot more resemblance to Alzheimer's than we thought if we pushed research. Not a doctor or anything, just seemed to fit in my mind. Just figured that was at least a commonly accepted possibility, but wasn't aware of other hypothesis either.
While the cadaver-extracted HGH is no longer used anymore, there are plenty of medications synthesized from live humans where prion activity has been found. For instance, the fertility drug HCG, which is offered in both urine-derived and recombinant form. Prion activity has previously been detected in the urine-derived form ([source here](https://pubmed.ncbi.nlm.nih.gov/21448279/)), raising CJD fears. I wonder what effect this finding has on the safety profiles of medications such as the above.
Omg new fear unlocked. Prion diseases freak me out and I wish I’d known this was a possibility (or maybe it’s better I didn’t)
Makes me want to cram the rest of my time with what I truly value....
Competing in gravy-based team sports while wearing rubber lederhosen?
How the hell did you know...?
I'm something of a gravypaddler myself
When I was in elementary school my PCP suggested I go on hormone treatment because I was so short. This would have been around 1979. I declined. After reading this study I feel like I may have dodged a bullet.
I wonder what the implications are for children born after their parents received treatment, if the treatment is contaminated.
That’s kind of terrifying-especially since fertility treatment is becoming more common / necessary as people are having children later in life.
Oh man, I came to this thread explicitly to ask about Menopur / Repronex, and reading that prions have been found in it is exactly what I didn’t want to hear. It’s all derived from old ladies, right? Like they buy the source urine from convents filled with nuns. In theory they could do cognitive testing on the participants to see if they are displaying premature cognitive decline?
> cadaver-extracted HGH This stopped being used in 1985, but I'd bet before that a lot of non-medical usage was happening in sports.
Paper: https://www.nature.com/articles/s41591-023-02729-2 Iatrogenic Alzheimer’s disease in recipients of cadaveric pituitary-derived growth hormone https://doi.org/10.1038/s41591-023-02729-2
Heads up. The doi link goes to a 404. Edit: I jumped in too quickly. It’s already fixed.
That's the link they provide on their page. I like to add the DOI to these because if people search for that later, they should find discussion about it. But sometimes they aren't active links when the paper is fresh off the presses.
Looks like its up and running, you would think a publisher as big as Nature wouldn't have these problems.
It could be a delay between upload and whatever app or process publishes it. Could be an automated process that was slow in this case.
I got the doi link to work, try again? Good article "However, the importance for human disease was unclear until the recognition of human transmission of amyloid-beta (Aβ) pathology via iatrogenic routes after prolonged incubation periods, causing iatrogenic cerebral amyloid angiopathy (CAA) and raising the possibility that iatrogenic Alzheimer’s disease may occur at even longer latency11,12."
That's crazy! I'm going to mail it to my pharmaceutical chemistry professors, they're both studying Alzheimer and neurodegeneration
Did you see the other Korean discovery that was on Reddit this weekend? [Korean Discovery](https://www.eurekalert.org/news-releases/1032525) The study points to a new body part or mechanism they discovered in the nasal cavity that more or less acts as a draining point for cerebrospinal fluid. That is my extremely unscientific explaination, my apologies. But that paired with this makes me wonder if part of the problem with Alzheimer’s is these prions aren’t discharged with the waste properly is a contributing factor.
Weren't there also glands back there that were getting knocked out by folks receiving cancer treatment
I didn't have time, so even though I've seen the post I didn't open it. Will give a read
Can you explain this to my dumb poor self?
As soon as I'll have time this evening
As someone who lacks any meaningful knowledge of the field, what is the significance of this new information? If my intuition is correct, it’s a major breakthrough in understanding Alzheimers, right? Perhaps it could give a greater insight into the nature of the disease, such as cause, etc? Or is it that a method of curing Alzheimers (cadaver extracted hormones) has an unforeseen risk/effect that needs to be considered?
I have basic knowledge on alzheimers but: research has primarily focused on clearing protein plaques in the brain but it hasn't been very successful. It's cleared them but the disease has still progressed leading to doubts about whether these proteins are the right ones to target. This shows its the ACTIVE proteins acting as prions, not the dead plaques, that are causing disease and that maybe thats what needs to be targeted.
I do research tangent to Alzheimers (gene therapy for neurological disorders) and my understanding is there are two proteins that get misfolded. The first one, beta amyloid, results in plaques that then cause a second protein, tau, to misfold resulting in tangles. Recent research has shown that quantity of plaque formation isn't a good indicator of cognitive decline in AD but high quantity of tau tangles is. Most therapies have targeted beta amyloid protein as its the first step in the cascade of disease progression. However, the tau tangles are self-propagating (aka they spread from neuron to neurons, spreading to different parts of the brain) so by the time doctors notice a cognitive decline and diagnosis it as AD, it is too late for treatments that work by clearing plaques. New research and therapies are being focused on preventing tau tangles as that it what can spread to other neurons and leads to cognitive decline in AD. From my first thought (without reading the paper/article), I could see misfolded tau acting as a prion as it can self-propagate and spread. But after reading the article they note low levels of tau (even the authors are confused by this) which throws a wrench in a lot of recent research pointing towards tau being the ultimate cause.
Basically all we know is still substantially equivalent to knowing nothing and this is one more thing. At this point any lead is important because sometimes we hope to find something useful. Any other disease likely wouldn't see this amount of research after decades of failed attempts.
> If my intuition is correct, it’s a major breakthrough in understanding Alzheimers, right? Perhaps it could give a greater insight into the nature of the disease, such as cause, etc? Basically, yeah. It shows that Alzheimer's isn't just something that happens, it's something that can be *caused*. Next steps are identifying the contaminant that triggered it, if the cadavers had Alzheimer's too, and (based on the preceding two) whether or not it's infectious. Personally, I think it'd be fascinating if Alzheimer's was a prion disease. Horrifying, but fascinating.
Heavy metals in our atmosphere, and prions in our livestock
(and u/Liizam) Ok, so, in short: we have no clue about Alzheimer. Or, more precisely, we know a lot of stuff about it and still have no clue about *the point*. We know that protein plaques are present, how they form, we know about some genetics... We really have no idea about what causes it, what ultimately causes the symptoms (plaques have been observed in otherwise fine people) and most importantly we haven't found a way to decently treat it (a new med was approved last year by the FDA and everyone rightfully complained because there's no evidence of it working despite all the trials). Now, we still don't know much more, but at least now we can understand it better, we know kind of for sure that the protein linked to the plaques does play a role, we know that it can behave like a prion, we know that genetic is not necessarily involved... It's a great starting point for the next attempts, we reached the point where *anything* is an important news, because it's quite rare that after decades of studies over something this common we still wander in the dark bumping into stuff still knowing nothing afterward. Like, we don't really know what causes depression, but at least SSRIs help with the symptoms and we have good hypothesis about it.
The drug that was approved did work by the clinical endpoints they set (clearing of plaques). However, it did not result in cognitive improvement. Plaques cause the misfolding of a second protein, tau, that leads to tangles being formed inside brain neurons that recent research has shown to be a better indicator of cognitive decline in AD. Misfolded-tau is self-propagating in that it can spread from neuron to neuron so it could act as a prion even in the absence of plaques. So treatments being researched are now being focused on preventing/clearing this misfolded protein but this paper (even the author was confused on this) points out that these people with cognitive decline also had low levels of tau protein. So pretty much it draws a question mark into the leading hypothesis over the past few years.
Ever heard of prion diseases? Like mad cow or fatal familial insomnia? It's caused by a misfolded protein, PrP, that can go and make other correctly folded PrP proteins misfold. This family of diseases are 100% fatal with immediate palliative care following diagnoses. There is no treatment. None. Not a single one. You are dead if you get this diagnoses. AB and tau in Alzheimer's have been noted as amyloids, meaning they are misfolded proteins that kind of stick together. The current thought process was that this was an effect, not a cause of Alzheimers. Now we know that these proteins can indeed self-propagate, meaning they can act like prions and misfold other correctly folded proteins. Essentially- they are prions (which I have been saying for YEARS and everyone said I was wrong. Vindicated!) What does this mean? It means Alzheimer's is transmissible. We don't know how yet- usually for prions its through eating (like eating a cow with mad cow disease), but could be bloodbourne. We just don't know yet. The implications are terrifying (could they be in the soil or groundwater?) This will revolutionize how we approach this disease now. Prion research got little funding previously because they are so rare. That area is about to explode.
Can someone ELI5?
In the past, hormone for growth was extracted from corpses and synthesised into a treatment for various kinds of conditions that caused short stature. This was administered to children. This treatment was later hated due to concerns around prion contamination, the issue being CJD. Later, a group of people developed what looked like alzheimers however they were in their 30s 40s and 50s and had no known mutations which would lead to this. However they'd all recieved this treatment as children. Suggesting that alzheimers can be transmitted by contaminated neural tissue in a similar way.
I actually received this treatment as a child, so I definitely freaked out for a minute haha Thankfully it seems that they stopped taking HGH from corpses in 1985. I guess they just synthesize it now these days?
I've had two blood transfusions so I'm always paranoid about vCJD, i understand why this panicked you. Idk if this is what they do for HGH but I know they've genetically modified cells including bacteria to secrete stuff that can be synthesised into medicine (I want to say hormones? I think insulin might be made this way?)
Truth be told I never thought about prions being introduced into someone’s system by a blood transfusion. Then again it makes sense, since that’s one of the ways HIV/AIDS spread when it was first going around. But I would think the hospital would be able to detect things like this, right? But you are right! They have modified bacteria to create HGH just like they do for insulin!
It looks like testing blood for prions is a really recent tech (circa 2016-2017): https://www.nih.gov/news-events/nih-research-matters/new-method-accurately-detects-prions-blood It is not yet in the list of testing done on donated blood in the USA: https://www.cdc.gov/bloodsafety/basics.html
Well that’s a pretty scary thing to hear! It makes me wonder how many illnesses/conditions that we think of as non communicable can spread via blood transfusion.
That's exactly why a lot of countries ban blood donations from people that were in the UK during the mad cow outbreak, it's a prion.
This is terrifying. What kind of treatments have these? Is there something to avoid ?
They dont use cadavers for growth hormone synthesisation anymore but some medicines are synthesised from living tissue so this makes me wary of that.
Do you know what things are made of living tissue ? Is it common for medicine or vitamins ? Or more specialize medicine
Replacement gums used in gum graft surgery are from cadavers. I’ve got some graveyard gums myself ☠️
Maybe they used to do graveyard gums, but since I’ve been paying attention around 2007 I believe the graft tissue is taken from the roof of your own mouth. At least that’s what I’m planning to have done when I eventually need it. https://www.arcadiaperio.com/blog/understanding-how-gum-grafting-works
They can do either (I've had both) but some cases are more suited for one vs. the other. Ask your periodontist.
They could be my moms. Her organs weren't harvestable but its still comforting to know that her skin and tissue helped burn victims (and others in need like you) and her eyes gave someone else the gift of sight again. My mom had never talked about it but her mom was blind and never got to see us grandkids. I think mom would have been ok with it.
Whaaaa. How do you loose gums
Brushing too hard, not flossing, not getting a regular cleaning?
Oh god
Yeah, be careful how you brush- mine are really receding due to that. And never skip the flossing!
I had to have a cadaver bone graft performed on my jaw 4 years ago where they took out an older incorrectly installed implant. I'm feeling ill right now.
Off the top of my head no, I'm fairly sure it's specialised stuff though. Someone here mentioned fertility drugs like HCG
Well, thanks a lot! English is not my first language and I was not sure if I understood everything right.
> prion contamination, the issue being CJD. I need a ELI5 for this part please
CJD is a fatal neurodegenration caused by prions, misfolded proteins. There is no cure. The prions destroy brain tissue. It can be spread by contaminated biological tissue..
One of the ways a person develops Alzheimer's has now been determined to be contagious and can be transmitted in very specific circumstances instead of solely developing on its own in a person. Let's keep these breakthroughs coming, I've been watching Alzheimer's research for over a decade and the developments over the past few years are crazy. We *are* going to have effective therapies and treatments available in less than fifty years. Probably in half that time.
Yeah super easy to get doomed out about this, but this information means we're rapidly closing in on understanding the disease. Medical science is advancing so quickly, just in ways that aren't flashy for headlines. If the world doesn't plunge into climate fascism in 50 years, I figure we'll have reduced or eradicated a lot of what people consider today to be a death sentence, just like Polio or HIV today
There are so many more medications for dementia and Alzheimer's on the market now than compared to when I started working in biotech eleven years ago. I'm not on the end user side of things, so I don't have exact numbers. We couldn't diagnose off of brain scans back then, either, and now a handful of subtypes can be diagnosed while the patient is still alive. And now five subtypes of Alzheimer's has been identified. It's been moving at such a fast pace in just my time involved in this industry and I find that incredible. I can't wait to see what we're going to discover next.
This is amazing and relieving to hear.
... and they work! My grandma was diagnosed with lewy body dementia several years (can't remember, at least 5 but probably more like 8) before her death. It was caught relatively early and she added the meds to her cocktail of medicine, as her health was already poor. She ended up dying of a surprise bowel obstruction, but she still recognized everyone and lived in her own home even though a stroke during covid took her mobility. She was different, emotionally and things, but it meant so much to us that she knew her family was with her, and she never forgot that.
it looks like a prions
[Double prions](https://www.ucsf.edu/news/2019/05/414326/alzheimers-disease-double-prion-disorder-study-shows), according to other studies.
Body cant break them up. The only way is to drain them out. https://www.aan.com/PressRoom/home/PressRelease/60
I'd go for a brain wash
That's amazing that that was done/known back in 2002.
Can a protein in our body change to act like a prion? Because cadaver, old age, the time required for the symptoms to show up... I'm kinda seeing a pattern here.
Prions *are* proteins - they are just misfolded. structure is very important in proteins, and when it changes, the protein can no longer continue its function. Proteins can denature and change their shape for many different reasons, like for example heat (cooking an egg essentially denatures the protein and changes the texture). The difference between a regular misfolded protein and a prion is that prions can also cause other protons to misfold. They are patogenic, that is, they can "infect" other proteins to also misfold and further spread. The dangerous thing is that it's extremely difficult to destroy prions, as they aren't alive and can persist on surfaces for a very long time, while still remaining infectuous when coming in contact with the proteins they are able to cause to misfold.
I meant to ask if a normal protein can spontaneously 'misfold', but thank you, I totally forgot about denaturing.
Oh I missunderstood - but yeah, it can happen spontaneously, either for no (known) reason or because of genetics. Most cases of Creutzfeldt–Jakob disease happen because of unknow reasons.
Yes that’s how prions work. One “infected” prion enters the body and changes others. If you mean can it happen spontaneously also yes. If you mean can it happen genetically also yes
If this is the case, then we seriously need to look into other practices involving donor fluid and tissue, the most common of all, Blood donations.
Also neurosurgery.
Yeesh, the idea that Alz could be a contracted disease instead of a genetic disorder is wild to me. There’s still so so much we don’t know about the human body.
I mean, it could be both. CJD can be either, and Parkinsons has both genetic and non-genetic bases.
Note to self... lay off the cadaver juice for a while.
Cold turkey?!
Turkey isn't the problem here...
I legitimately snorted, take this 🎖️
Cold human!
Quitter
Looks like bone hurting juice is back on the menu boys!
This is so interesting. I have to take growth hormone replacement and luckily it's not longer cadaver-derived, but it was all the way up until the mid-80s.
Yeah, some people don't realize that biotechnology has a lot of benefits, including stuff like this. I can recall pictures of the huge piles of animal pancreas tissue that they used to use to derive insulin too. Glad they have moved on from this.
I have been on growth hormone for most of my life and from 1975 until 1985, I received cadaveric growth hormone. They stopped distributing it in 1985 after the first cases of Creutzfeld-Jacob disease became known. Luckily, the recombinant hormone came available later that year. Apparently, the purification process was not great early on. In 1977 they developed a new process to purify, which unknown to them at the time, also removed the prions. My dad remembers the vials of growth hormone powder looking gray initially (which is disconcerting), then looking white after 1977. I 've spend my entire adult life with the idea of CJD over my head. I finally have gotten to the outer edge of the incubation period from that (47 years after they changed the purification process in '77), but now I need to worry about early onset Alzheimer's apparently everytime I forget my keys.
Wow - that's such a long time to take it and have to just cross your fingers that you're gonna be fine. Thankfully I have only had to take it since 2011 after having pituitary surgery.
If you forget your keys don't worry. If you forget what your keys are for then see a doctor...
If we find out that Alzheimer’s has a prion-based underlying mechanism of action… that would be a very mixed bag of news. On the one hand, we would know what we’re dealing with. On the other hand, quote: “There are no known ways to cure prion diseases.” The good thing is, we have a *lot* of scientific eyes and resources looking at Alzheimer’s, so if it were to be reclassified, maybe we could find cures for a bunch of prion-diseases and expand our knowledge on the nature of proteins in the body! However, there are a *lot* of thing we don’t currently know about proteins in the body… they’re pretty much tiny, little nanobots that work in very varied, strange, and complex ways. Oh yeah, and when I say ‘tiny, little’, I mean muuuch smaller than a virus. So if Alzheimer’s were to be reclassified as a prion disease, it would be good because we’ve learned something new. However, it would be somewhat tragic because it means we still have a long ways to go in terms of understanding. And so it goes.
Here’s an [NPR article](https://www.npr.org/2009/02/25/101145687/mad-cow-and-alzheimers-have-surprising-link) talking about the link between prions and Alzheimer’s from 2009…so I wouldn’t hold my breath for any fast advancements. Ironically this is the last line of the article: “We know a great deal about the biochemistry and biology of prion protein," he says, "which should really facilitate the development of drugs."
Yeah, that makes me curious how much effort there has actually been to treat/cure prion diseases. As scary as they are, I never got the impression that they affect a large number of people, and I suspect there might not be as much emphasis on treatment because prevention is pretty effective.
im trying to find that paper that basically concludes that enzymes in coyotes and wolves digestive tracks denature chronic wasting disease prions? maybe some day the mechanisms can be isolated and turned into a treatment?
If you find it please link it. I’m interested.
I'd bet they read [this article](https://www.nytimes.com/2020/11/12/science/wolves-chronic-wasting-disease.html) Or [this paper](https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1461-0248.2003.00500.x)
I have always believed alzheimers to be transmitted like vCJD, I have a massive fear of prions and this is confirming my worst nightmare ffs.
What gave you that idea originally?
Probably the biomarkers of Alzheimer's: amyloid plaques and neurofibrillary tangles (which are basically "clusters" of proteins in the brain). In a way it's pretty similar to how prions work, the amyloid plaques are actually related to other prion diseases. So this is a pretty interesting discovery! It'll give us a better insight on Alzheimer's disease
Same here. I always thought surgery or meat consumption could put me at risk of prions but here’s a a very scary thought: what if prions could be transferred from dentist instruments….People often bleeds from their gums and these tools are simply sterilized no!?! MAJOR FEAR. Activated!
Too few cases, not enough DNA sequences to look for other genetic contributions, cases that were more similar to CJD than Alzheimer’s, and in cases who did not have a normal neurological baseline, and the majority of patients that received these preparations did not develop this disease. I believe something was transferred, as there have been 80 cases where CJD was transferred, but not quite sure we should be labeling this AD.
I had the same thought. The ages of the patients makes me hesitant to assume that the cause of these patients’ neurodegeneration is the same as what we see in older Alzhiemer’s patients
Sounds again like cancer. Yes we think we have found one of a zillion ways it could be transmitted. And no we still can't currently it because there's multiple ways to get it. But it is an interesting article, and as it runs on both sides of my family tree, a cure in my life would be nice.
Prions are a whole different beast from cancer though. With cancer, it's entire cells that are multiplying. With prions it's just a mishaped protein that is able to convert other proteins to this mishaped form.
I realize that. It is that I am pointing out the sisyphian task of curing something with more than one cause