We work in neurostimulation and sleep, and collaborate with Alzheimer's researchers.
The Amyloid hypothesis is not disproven, it is still ONE of the primary candidates for AD.
The problem with any Alzheimer's research is that the disease is still not well understood. It is likely that multiple diseases are being bundled in as a single disease. The tests for AD, are somewhat rudimentary. Beginning with psychological and neurological tests, the blood work to rule out other conditions, followed by a PET scan to look for brain atrophy, and CSF measures for amyloid and tau levels.
It seems almost like they're basically ruling out any disease we can actually measure for and then if it isn't one of those, it's AD.
Does this mean the Amyloid hypothesis is wrong? Unlikely. Is it incomplete? Absolutely!
But articles shouting that all the research should be thrown out are not helpful .
The AD community know that they don't understand the disease, and though therapeutics have been mostly focused on amyloid and tau, research into how the disease works continues.
> But articles shouting that all the research should be thrown out are not helpful .
Good thing OP isn't one, then. In fact it makes a pretty similar point: all the non-amyloid research also should not have been thrown out. Or rather, killed before it got that far; you can decide whether that's equivalent or worse.
Not thrown out - just not funded. But that is a question more re: how great the judgement of the NIH program managers/officers are, as well as whether there should be a healthier alternative funding mechanism to NIH dominated research funding for academia...
I.e. if one has a good pitch for an experimental direction, in an ideal world, the program managers would be an equal opportunity funder and arrange for diverse study sections evaluating proposals etc. But there can only be so many NIH program managers, maybe even less in today's DOGE-ey/RFKj climate, so then in another ideal world, there would be private funders, foundations, etc. But no one wants those because they're not structured w/ matching/overhead funds for academic centers. ergo, maybe the government should fund matching for private research foundation grants...but one would assume government that is in a funding, Keynesian mood vs. a cutting-the-budget mood...
Could the Amyloid/tau hypothesis be a cart before the horse situation? It is my understanding that the current hypothesis is that the buildup of these proteins causes Alzheimer's. Could it be that Alzheimer's causes these proteins to build up?
Its not the only disease this has happened to either. ME/CFS has been railroaded by European governments that funded only psychological research despite numerous pathological findings and better theories of the disease, this prejudiced treatment started in the 1970s and persists to this day including the corruption of the PACE trial results which researchers tried to hide the data of.
For a long time, fibromyalgia was only diagnosed by ruling out everything else. There was a lot of 'It's all in your head.' Last year they developed an actual blood test for it that detects the wonky immune system response.
One infuriating thing about PACE is that even the fraudulent results only showed a 22% recovery rate.
For a disease as serious as ME/CFS, a treatment with a 22% recovery rate is far from good enough. Even if PACE stood up to scrutiny it wouldn’t have made sense to give up on finding better treatments.
This argument gets invoked a lot when it comes to medical dishonesty, but I really don't think it applies in the case of ME/CFS. If we could find the pathology behind the condition, there is huge money to be made in pharmaceutical treatments. Just look at the enormous amount of money being made treating auto-immune illnesses with Humira/Skyrizi/Xeljanz/etc, treating diabetes with GLP-1 agonists and CGMs, and treating obesity with GLP-1 agonists (and depression before all that!). Sometimes treating the chronically ill is the most profitable option.
he was not in the trenches in 2003. in 2003 we were working in an Alzheimer's lab and everyone in our lab at least was expressing suspicion that there was something wrong with the hypothesis. pretty much every internal lab meeting started with "the amyloid hypothesis is... [this statement exists because our funding stream] though it is not conclusively proven, wink wink"
Granted, I have heard a scientist (in an unrelated field, I think it was some astronomical NPR interview) describe science as a bit like a supertanker...there usually is some prevailing thing that everyone believes in, but as contrary evidence piles up, the direction slowly turns.
I guess my own question is whether Alzheimer's/amyloid thinking was atypically stuck on one hypothesis, vs. is this just the slow pace of progress as usual for a given field? I mean...it's not like the amyloid deposition isn't there...
I only play a AD expert on TV (haha I jest...I like to say this because I had no intention of specializing in this when I was training but, hey, in the real world, you have to treat the "market" that rolls in the door....). I work more in the Parkinson's world, and while I would say there are cliques, which do affect who gets NIH (or used to get...I have no idea what's going on there now...), I can't say there's one prevailing "cabal" that's obsessed with any one direction. the bigger issue is that current Parkinson's research is a bit scattershot in too many directions.
My other pet peeve is somewhat unrelated, where the article mentions other directions like neuroinflammation and oxidative stress; the problem is these are also vague/broad topics, that have been thrown around like panaceas for every disease from head to toe; my own superstition is that when a new drug candidate comes out for "neuroinflammation" or "oxidative stress", I'd bet a healthy bunch of nickels it won't amount to much.
His blog has a category just for discussing Alzheimer's, and he's been talking about ever since he started blogging. So here's a post from 2002 where he points out (somewhat obliquely) that amyloid isn't a proven hypothesis: https://www.science.org/content/blog-post/alzheimer-s-vaccin...
> This is looking like one of the crazy ideas that just might work - stipulating, for the moment, that amyloid really is the cause of Alzheimer's. . .
Which is the only good take… if there wasn’t “something promising” with the idea, people wouldn’t have kept at it. There’s only so much time you’re going to waste on pure fantasy before you move on. The whole ordeal had me quite upset as I was supporting studies looking at this, and the patients are beyond desperate for any treatment. None of us got rich.
sunk cost, stockholm syndrome, refusal to change mental models, "it is hard to get a man to understand something when their salary depends on it not being true"
amyloid experiments, especially biophysics experiments, are really fucking hard and really fucking expensive. like, months of hundred hour weeks hard. then it usually fails. so when you burn years of this cycle to find a consistent result (artefact or not), its crazy hard to let go of it.
if you want a very rare example of someone who did the right thing:
45 citations in 10 years. how many amyloid researchers do you think are aware of this problem with plasticware being published. and probably most "know" it from lived experience, but they say "fuck it, i need to finish my phd/postdoc" and just scramble to push out any result, plastics being problematic be damned.
the only thing that could remotely stop the nonsense from continuing is if the NIH had the balls to take this result and issue guidance to halt all amyloid research that doesnt take plastic use into account. but 1) the program managers are not smart enough to do something like that and 2) such a deep challenge to the research agenda would shake the system way too much from the top AND the bottom. just easier to continue being a bureaucrat with a nice salary and a very "mid" approach to science.
There's a lot of researchers in a lot of roles and it turns out finding targets is just one of those roles, the rest focus on optimizing therapies against those targets and they like having well defined targets to work on.
Every degenerative CNS disease is caused by death of non replicating cells. By definition, the cure of such diseases is equivalent to immorality. This already highlights the importance and difficulty of such achievement.
The amyloid hypothesis seems too simple and superficial to account for a decades long process (it is speculated that Alzheimer's starts up to 20 years before symptom onset). The ultimate problem is to find the underlining cause(s) and not correlations.
Anti-science types keep holding this up as some kind of 'gotcha' or as a waste, but in the end it shows that the scientific method and the scientific establishment work efficiently.
Despite even intentional fabrication, the truth of it was found in a few years and the field marches on.
It was published and cited. 45 in 10 years is a reasonably okay citation count. What's the problem?
Science is slow and consensus based. Ideas are put forth, tested, and replicated. Eventually a consensus is formed. If enough new contrary evidence is collected a new consensus can form. The article you linked is not consensus changing, but it adds weight on the scale of change, and clearly it worked. Mission accomplished.
Science does not turn on a dime. It took many decades for Lynn Margulis's endosymbiosis theory to catch on, but it did. The evidence was eventually undeniable, and the consensus changed.
This AD story is just another slow consensus change. We still don't know exactly how AD works. We still know amyloid is involved somehow. We now know amyloid isn't everything.
The system works. It's just slower than you like it to be.
I guess it depends where you set the starting point. Was it a dead end exacerbated by fabricated data? Yes. Did the system correct itself (relatively) quickly. Yes.
HN (and Silicon Valley) has a contingent of people that want to attack the credibility of the scientific community so that they can present their own (usually very flawed) conclusions as being legitimate.
well that's a funny way to put it. i assure, there is a contingent of the scientific community that would like to attack the credibility of the scientific community to discredit the actually very flawed conclusions of the scientific community.
Readit News
The Amyloid hypothesis is not disproven, it is still ONE of the primary candidates for AD.
The problem with any Alzheimer's research is that the disease is still not well understood. It is likely that multiple diseases are being bundled in as a single disease. The tests for AD, are somewhat rudimentary. Beginning with psychological and neurological tests, the blood work to rule out other conditions, followed by a PET scan to look for brain atrophy, and CSF measures for amyloid and tau levels.
It seems almost like they're basically ruling out any disease we can actually measure for and then if it isn't one of those, it's AD.
Does this mean the Amyloid hypothesis is wrong? Unlikely. Is it incomplete? Absolutely!
But articles shouting that all the research should be thrown out are not helpful .
The AD community know that they don't understand the disease, and though therapeutics have been mostly focused on amyloid and tau, research into how the disease works continues.
Good thing OP isn't one, then. In fact it makes a pretty similar point: all the non-amyloid research also should not have been thrown out. Or rather, killed before it got that far; you can decide whether that's equivalent or worse.
I.e. if one has a good pitch for an experimental direction, in an ideal world, the program managers would be an equal opportunity funder and arrange for diverse study sections evaluating proposals etc. But there can only be so many NIH program managers, maybe even less in today's DOGE-ey/RFKj climate, so then in another ideal world, there would be private funders, foundations, etc. But no one wants those because they're not structured w/ matching/overhead funds for academic centers. ergo, maybe the government should fund matching for private research foundation grants...but one would assume government that is in a funding, Keynesian mood vs. a cutting-the-budget mood...
Research fraud in medicine is alarmingly common.
For a disease as serious as ME/CFS, a treatment with a 22% recovery rate is far from good enough. Even if PACE stood up to scrutiny it wouldn’t have made sense to give up on finding better treatments.
Like, sure, shoot for 200% cure rate, but even a success rate of 1% cured of a previously unrecoverable situation is insanely informative.
- The great brain clearance and dementia debate - https://www.nature.com/articles/d41586-025-00962-y (2025)
- The Devastating Legacy of Lies in Alzheimer’s Science - https://www.nytimes.com/2025/01/24/opinion/alzheimers-fraud-... (2025), referencing the book Doctored https://en.m.wikipedia.org/wiki/Doctored_(book)
- The maddening saga of how an Alzheimer’s ‘cabal’ thwarted progress toward a cure for decades - https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte... (2019, by the late Sharon Begley)
https://www.science.org/content/blog-post/reaction-alzheimer...
I guess my own question is whether Alzheimer's/amyloid thinking was atypically stuck on one hypothesis, vs. is this just the slow pace of progress as usual for a given field? I mean...it's not like the amyloid deposition isn't there...
I only play a AD expert on TV (haha I jest...I like to say this because I had no intention of specializing in this when I was training but, hey, in the real world, you have to treat the "market" that rolls in the door....). I work more in the Parkinson's world, and while I would say there are cliques, which do affect who gets NIH (or used to get...I have no idea what's going on there now...), I can't say there's one prevailing "cabal" that's obsessed with any one direction. the bigger issue is that current Parkinson's research is a bit scattershot in too many directions.
My other pet peeve is somewhat unrelated, where the article mentions other directions like neuroinflammation and oxidative stress; the problem is these are also vague/broad topics, that have been thrown around like panaceas for every disease from head to toe; my own superstition is that when a new drug candidate comes out for "neuroinflammation" or "oxidative stress", I'd bet a healthy bunch of nickels it won't amount to much.
> This is looking like one of the crazy ideas that just might work - stipulating, for the moment, that amyloid really is the cause of Alzheimer's. . .
https://direct.mit.edu/books/book/5216/How-Not-to-Study-a-Di...
The core problem is much older than stated in this focused review.
amyloid experiments, especially biophysics experiments, are really fucking hard and really fucking expensive. like, months of hundred hour weeks hard. then it usually fails. so when you burn years of this cycle to find a consistent result (artefact or not), its crazy hard to let go of it.
if you want a very rare example of someone who did the right thing:
https://scholar.google.com/citations?view_op=view_citation&h...
45 citations in 10 years. how many amyloid researchers do you think are aware of this problem with plasticware being published. and probably most "know" it from lived experience, but they say "fuck it, i need to finish my phd/postdoc" and just scramble to push out any result, plastics being problematic be damned.
the only thing that could remotely stop the nonsense from continuing is if the NIH had the balls to take this result and issue guidance to halt all amyloid research that doesnt take plastic use into account. but 1) the program managers are not smart enough to do something like that and 2) such a deep challenge to the research agenda would shake the system way too much from the top AND the bottom. just easier to continue being a bureaucrat with a nice salary and a very "mid" approach to science.
The amyloid hypothesis seems too simple and superficial to account for a decades long process (it is speculated that Alzheimer's starts up to 20 years before symptom onset). The ultimate problem is to find the underlining cause(s) and not correlations.
Despite even intentional fabrication, the truth of it was found in a few years and the field marches on.
45 citations in 10 years for a paper pointing out a major systematic flaw in almost all foundations of amyloid reserch. the system is not working.
Science is slow and consensus based. Ideas are put forth, tested, and replicated. Eventually a consensus is formed. If enough new contrary evidence is collected a new consensus can form. The article you linked is not consensus changing, but it adds weight on the scale of change, and clearly it worked. Mission accomplished.
Science does not turn on a dime. It took many decades for Lynn Margulis's endosymbiosis theory to catch on, but it did. The evidence was eventually undeniable, and the consensus changed.
This AD story is just another slow consensus change. We still don't know exactly how AD works. We still know amyloid is involved somehow. We now know amyloid isn't everything.
The system works. It's just slower than you like it to be.
I agree but 16 years is still significant. It represents 5% of the modern medicine era.
Working as intended.