They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable.
Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most guesses work to some degree to keep pharma alive - otherwise nobody would fund the business.
Edit: Google the in the pipeline blog. This and other have discussed this at length.
I thought despite the fraud, it's still the best model we have[1]? The fact there was fraud doesn't mean the model is immediately incorrect. At best, it means its foundations are shakier than we thought, but it's not a slam dunk repudiation.
The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis.
What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza don't.
Now people can ask questions about why those particular vaccines affect dementia while others don't. And suddenly we have falsifiable tests.
Now we can subject all hypotheses (including Amyloid) to stronger scrutiny.
The major problem has been lock-in of the Abeta 42 peptide fragment as the cause. This monomaniacal focus was rewarded by grant awards to team players.
Karl Herrup has a terrific book on the topic How Not to Study a Disease — The Story of Alzheimer’s from MIT Press (2021, ISBN 9780262045902). He did not win many friends but I think he is right.
The consensus now is that many factors contribute to the heterogeneous diseases we now call Alzheimer’s.
The article (or I guess more accurately "podcast transcription") seems to be saying that this lock-in essentially happened due to fraud, since some of the data was intentionally doctored to get the intended result. One of the guests seems to be an author of a different book about this (with the other guest being the scientist who apparently uncovered this). I can't personally attest to the accuracy of anything they said, but they're at least alleging that it was a lot less benign than it sounds like you're describing.
The focus is definitely on scientific fraud, but what makes the fraud so easy in this case is singing and selling the same song that the big teams are singing and selling. You can fly under the radar AND get funded, and if you are “lucky” become an ultra big shot like Masliah at NIA.
I don't buy the fraud explanation as the full explanation. Other areas of medicine (stem cell) has had bigger incidents of fraud on top of other major headwinds, and still has made more progress.
Fraud is everywhere and we still move forward in most arenas.
"Despite being described as a “cabal,” the amyloid camp was neither organized nor nefarious. Those who championed the amyloid hypothesis truly believed it, and thought that focusing money and attention on it rather than competing ideas was the surest way to an effective drug.
It has not worked out that way. Research focused on amyloid, and the development and testing of experimental drugs targeting it, have sucked up billions of dollars in government, foundation, and pharma funding with nothing to show for it. While targeting amyloid may or may not be necessary to treat Alzheimer’s, it is not sufficient, and the additional steps almost certainly include those that were ignored, even censored. Probably the most shattering turn came in March, when Biogen halted the study of what proponents called the most promising Alzheimer’s drug in years — an amyloid-targeting antibody."
I still refer to this article seven years later. Groupthink in the medical research space sets back progress by decades. And it's not just Alzheimers. The FDA's approval process is stymied by a CYA culture that fails to adopt the risk profile it needs to in order to potentially save large contingents of sick and dying.
'Science progresses one funeral at a time...' It is often the case that an entire field is led by a few influential people and until they leave others can't get the air they need to make real progress.
> gatekeepers directly or indirectly control research funding.
Perhaps funding like public grants could be controlled by few? Should not the case for private money?
Relatively common health issues older people tend to get fair amount of private funding after all.
Rich people tend to be older and they are lot more likely to see amongst their friends and family Alzheimer's and Parkison's or even cancer and so forth and be worried about it and thus donate money to them.
In somewhat related (i.e. old people health concerns) life extension research gets all kinds of wacky non traditional research lines get funded all the time, I don't understand why would Alzheimer's would be any different.
If you're a wealthy person lacking a neurobiology background, how do you decide which research efforts are the most promising? Which labs do you back?
Generally, you rely on experts.
Who typically became experts by adhering to the conventional wisdom set by gatekeepers.
"Science advances one funeral at a time" feels apt.
Sadly, the problem isn't confined to Alzheimer's.
Whenever only a few people decide what is "right," the same pattern of stifled innovation will generally manifest itself not by design or from malice, but because it's hard for a small group to be 100% right on what works and what doesn't -- especially on matters as inscrutable as neuroimmune diseases.
Life extension seems like the kind of thing that can get private funding with relative ease specifically because they aren't trying to compete with the government. There are a lot of private foundations that give out grants too though.
Life extension in the private sector is dominated by hocus-pocus and unwarranted optimism. The genetics of mortality is amazingly complex. See this open access monster paper that came out in Nature this week—admittedly “in mice” on mortality and genetic of longevity.
Type-3 diabetes? It's degraded endocrine and cardiovascular functionality. Basically, your enzymes stop producing -- things like testosterone and insulin. Your lungs stop working as efficiently, and your brain just gives out.
If you're looking to beat type-3 diabetes, you need to have a daily routine of exercise while you're young to keep these systems in shape when you're old.
You also don't need to belong to any marginalized groups, as ACEs tend to wear your body out over time -- breathing, kidneys, and heart in particular. People with traumatic childhoods (bullying, abusive parents, etc) have a huge risk of dying of dementia -- if their kidneys don't give out first.
Alzheimer’s is a good example of a disease where we don’t have great scientific understanding on the underlying causes, but that doesn’t stop individuals from believing they understand it better than the scientists.
Actual Scientists are calling it Type-3. But these are the same scientists that are actually reversing Type 2 diabetes without expensive drugs. Of course they exist outside the pharma narrative, and they don't have any uncurious attack dogs willing to defend their narrative-busting results.
Are recurrent childhood neglect and abuse events not an antecedent to mental health morbidity in adulthood, which then creates missed opportunities for growth and necessitates and the need for the use of medications?
I think you’re making a giant leap from A to Z and missing a whole bunch in between.
All I know is that people with higher ACE scores have higher dementia rates. And that higher ACE scores are linked with heart failure, lung failure, and kidney failure.
Stress ages the body. Homeless people can age several years, being on the streets for just a few months.
I've also seen numerous people in these upbringings die in their 50s and 60s from kidney failure. My stepdad was one of them. My father too.
My father had a normal childhood, except he had a traumatic experience of shooting his twin brother while they were playing cowboys and indians. Spent his entire life blaming himself. Went through all the normal development phases. Not on any meds.
His body just started shutting down prematurely. It's common in people with those experiences. First, his breathing got bad. Then his kidneys. Then he started having heart problems.
And that's the pattern. Heart, lungs, kidneys. Which are all linked to the brain. And eventually lead to dementia-like symptoms. At least that's what the research on ACEs seems to point out.
Elaborating a bit - brain is hard to study since you can't easily take a biopsy of it (from a living person at least), and various brain scans are not great at identifying the stuff we care about.
The slow acting nature of it means also you have to wait a long time to see results of clinical trials; also because early stages are easy to miss that also means you are stuck studying people who are already pretty senile and thus might be beyond the point where you can make a big difference.
Ruxandra has a nice piece, focused on cancer, but the reasoning is basically the same here: biology is just really hard. Sometimes we get lucky but in general it's a long, slow slog.
I'm not saying I'm the best informed on this topic, but I thought the root cause has been known for a long time now as degraded endocrine and cardiovascular function.
That's also why Alzheimer's can take so long to develop. It's just one aspect that we've chosen to focus on because it's more clearly noticeable, but it cannot easily be treated in isolation from everything else. If it was, it would regress quickly without fixing the root causes.
We truly do not know the root cause. There are plenty of folks with "degraded" endocrine, cardiovascular, and both systems. Most of them do not develop Alzheimer's.
There is no single root cause. Many scientists have preferred to ignore this fact and that has been a serious problem. Everyone likes a simple story. Age-related diseases are not simple stories.
...because Alzheimer is a dormant side effect of a virus, not of a messenger chemical. But that doesn't go well in studies and "self populism" of what funded research wanted to hear.
If you study effects and not causes due to lack of measurements for reproducibility in any field of research, that's what comes out.
Also check out how the correlation on how it started by observing the Wales eligibility for mandatory shingles vaccination during an outbreak and the effect on that test group when it comes to alzheimer or dementia in their old age.
Note that shingles (herpes zoster) virus is a dormant virus for decades, and it's not really treated because of that.
Also note that this was only discovered because people died and their data set was publicized because of that, which I hope that can happen in an anonymous way due to it being invaluable for medical research.
Same scam and politics as the Ancel Keys lipid-heart hypothesis. Complete BS, ego and career protectionism, resulted in the deaths of millions and most people still believe that crap.
Its done substantially better than more common diseases like ME/CFS which very few have even heard of let alone know the symptoms of and receives almost no funding at all. Alzheimer's received a further $100 million of NIH funding earlier this year (https://www.alz.org/news/2026/100-million-dollar-alzheimers-...). That is 6 times the total funding for ME/CFS federally which is currently just 15 million and planned to decline.
The research went awry in Alziemer's due to fraud but its being funded at a reasonable level, a level many with Long Covid or ME/CFS or Fibromylgia would be very happy to see but doubt will ever happen. Funding of diseases is not "fair", it isn't based on number of sufferers * quality life years lost and we should be spending more on medical research generally. Alzeimers is one of the better funded diseases in the world.
No clue why you think chronic fatique syndrome and dementia ought to be treated as equally debilitating or serious by the medical community, but I'm sure you're the only person on this earth who holds that opinion.
Naturally, the far more terrifying and inexorable disease that is incurable and robs people of their entire personality and will affect most of us to some extent (dementia, if not Alzheimer's specifically) by the end of our lives gets more funding and attention, as it should. The way Alzheimer's has been researched and funded is diabolical, though, but you might pick any other of 200 serious progressive neurological disorders that are underfunded and underrepresented over... CFS. CFS isn't even fully accepted as a syndrome at this point - long COVID is probably more accepted as a real thing by practitioners at this point than CFS.
> long COVID is probably more accepted as a real thing by practitioners at this point than CFS
Isn't long covid just CFS that can be attributed to Covid?
If you accept that multiple viruses can cause "long <virus>" syndromes, of which long covid is just one example, it's plausible that CFS is really a cluster of syndromes, one category of which is these post viral syndromes. We just can't pinpoint the virus behind it every time because most viruses haven't been studied as much as Covid has.
They had a biological model. They had multiple drugs that were showed activity against that model, and effectiveness in humans. Problem was, the model was wrong. Pharma’s burned billions chasing this as it’s possibly the biggest market imaginable.
Whether it was fraudulent or just incorrect is a different question. We don’t know all of the details of human biology. We don’t even know what all we don’t know. Most guesses work to some degree to keep pharma alive - otherwise nobody would fund the business.
Edit: Google the in the pipeline blog. This and other have discussed this at length.
> Problem was, the model was wrong.
I thought despite the fraud, it's still the best model we have[1]? The fact there was fraud doesn't mean the model is immediately incorrect. At best, it means its foundations are shakier than we thought, but it's not a slam dunk repudiation.
[1] https://www.astralcodexten.com/p/in-defense-of-the-amyloid-h...
The Amyloid hypothesis persisted for so long because we didn't have any obvious counterarguments since it is so hard to do studies on the brain. Which also means that it's not a bad hypothesis.
What happened is we got the tools to start studying viral associations with other diseases and ... whooops ... suddenly there are associations. The shingles and RSV vaccines seem to affect dementia while others like influenza don't.
Now people can ask questions about why those particular vaccines affect dementia while others don't. And suddenly we have falsifiable tests.
Now we can subject all hypotheses (including Amyloid) to stronger scrutiny.
The major problem has been lock-in of the Abeta 42 peptide fragment as the cause. This monomaniacal focus was rewarded by grant awards to team players.
Karl Herrup has a terrific book on the topic How Not to Study a Disease — The Story of Alzheimer’s from MIT Press (2021, ISBN 9780262045902). He did not win many friends but I think he is right.
The consensus now is that many factors contribute to the heterogeneous diseases we now call Alzheimer’s.
The article (or I guess more accurately "podcast transcription") seems to be saying that this lock-in essentially happened due to fraud, since some of the data was intentionally doctored to get the intended result. One of the guests seems to be an author of a different book about this (with the other guest being the scientist who apparently uncovered this). I can't personally attest to the accuracy of anything they said, but they're at least alleging that it was a lot less benign than it sounds like you're describing.
The focus is definitely on scientific fraud, but what makes the fraud so easy in this case is singing and selling the same song that the big teams are singing and selling. You can fly under the radar AND get funded, and if you are “lucky” become an ultra big shot like Masliah at NIA.
I don't buy the fraud explanation as the full explanation. Other areas of medicine (stem cell) has had bigger incidents of fraud on top of other major headwinds, and still has made more progress.
Fraud is everywhere and we still move forward in most arenas.
Reminds me of schizophrenia. A hodgepodge of different things lumped into a single label of "broad class of things we don't understand"
https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarte...
"Despite being described as a “cabal,” the amyloid camp was neither organized nor nefarious. Those who championed the amyloid hypothesis truly believed it, and thought that focusing money and attention on it rather than competing ideas was the surest way to an effective drug.
It has not worked out that way. Research focused on amyloid, and the development and testing of experimental drugs targeting it, have sucked up billions of dollars in government, foundation, and pharma funding with nothing to show for it. While targeting amyloid may or may not be necessary to treat Alzheimer’s, it is not sufficient, and the additional steps almost certainly include those that were ignored, even censored. Probably the most shattering turn came in March, when Biogen halted the study of what proponents called the most promising Alzheimer’s drug in years — an amyloid-targeting antibody."
I still refer to this article seven years later. Groupthink in the medical research space sets back progress by decades. And it's not just Alzheimers. The FDA's approval process is stymied by a CYA culture that fails to adopt the risk profile it needs to in order to potentially save large contingents of sick and dying.
'Science progresses one funeral at a time...' It is often the case that an entire field is led by a few influential people and until they leave others can't get the air they need to make real progress.
TLDR: gatekeepers stifled exploration and innovation.
When a topic only has a limited number of experts, those experts become gatekeepers.
Those gatekeepers directly or indirectly control research funding.
Gatekeepers necessarily harbor biases, some right and some wrong, about how the field should progress.
For Alzheimer's, some gatekeepers were conflicted and potentially directed the field in the wrong direction. Only time will reveal AB42's true role.
It's easy to find fault in Alzheimer's.
It's harder to see the general solution to the gatekeeper problem, i.e., how to allocate resources in areas with limited experts.
> gatekeepers directly or indirectly control research funding.
Perhaps funding like public grants could be controlled by few? Should not the case for private money?
Relatively common health issues older people tend to get fair amount of private funding after all.
Rich people tend to be older and they are lot more likely to see amongst their friends and family Alzheimer's and Parkison's or even cancer and so forth and be worried about it and thus donate money to them.
In somewhat related (i.e. old people health concerns) life extension research gets all kinds of wacky non traditional research lines get funded all the time, I don't understand why would Alzheimer's would be any different.
If you're a wealthy person lacking a neurobiology background, how do you decide which research efforts are the most promising? Which labs do you back?
Generally, you rely on experts.
Who typically became experts by adhering to the conventional wisdom set by gatekeepers.
"Science advances one funeral at a time" feels apt.
Sadly, the problem isn't confined to Alzheimer's.
Whenever only a few people decide what is "right," the same pattern of stifled innovation will generally manifest itself not by design or from malice, but because it's hard for a small group to be 100% right on what works and what doesn't -- especially on matters as inscrutable as neuroimmune diseases.
Life extension seems like the kind of thing that can get private funding with relative ease specifically because they aren't trying to compete with the government. There are a lot of private foundations that give out grants too though.
Life extension in the private sector is dominated by hocus-pocus and unwarranted optimism. The genetics of mortality is amazingly complex. See this open access monster paper that came out in Nature this week—admittedly “in mice” on mortality and genetic of longevity.
https://www.nature.com/articles/s41586-026-10407-9
(I’m an author)
Type-3 diabetes? It's degraded endocrine and cardiovascular functionality. Basically, your enzymes stop producing -- things like testosterone and insulin. Your lungs stop working as efficiently, and your brain just gives out.
If you're looking to beat type-3 diabetes, you need to have a daily routine of exercise while you're young to keep these systems in shape when you're old.
You also don't need to belong to any marginalized groups, as ACEs tend to wear your body out over time -- breathing, kidneys, and heart in particular. People with traumatic childhoods (bullying, abusive parents, etc) have a huge risk of dying of dementia -- if their kidneys don't give out first.
Alzheimer’s is a good example of a disease where we don’t have great scientific understanding on the underlying causes, but that doesn’t stop individuals from believing they understand it better than the scientists.
Actual Scientists are calling it Type-3. But these are the same scientists that are actually reversing Type 2 diabetes without expensive drugs. Of course they exist outside the pharma narrative, and they don't have any uncurious attack dogs willing to defend their narrative-busting results.
True dat. But most of Europe calls it type-3 diabetes, because of the reasons given.
Are recurrent childhood neglect and abuse events not an antecedent to mental health morbidity in adulthood, which then creates missed opportunities for growth and necessitates and the need for the use of medications?
I think you’re making a giant leap from A to Z and missing a whole bunch in between.
All I know is that people with higher ACE scores have higher dementia rates. And that higher ACE scores are linked with heart failure, lung failure, and kidney failure.
Stress ages the body. Homeless people can age several years, being on the streets for just a few months.
I've also seen numerous people in these upbringings die in their 50s and 60s from kidney failure. My stepdad was one of them. My father too.
My father had a normal childhood, except he had a traumatic experience of shooting his twin brother while they were playing cowboys and indians. Spent his entire life blaming himself. Went through all the normal development phases. Not on any meds.
His body just started shutting down prematurely. It's common in people with those experiences. First, his breathing got bad. Then his kidneys. Then he started having heart problems.
And that's the pattern. Heart, lungs, kidneys. Which are all linked to the brain. And eventually lead to dementia-like symptoms. At least that's what the research on ACEs seems to point out.
I'm surprised that better science never resulted from that lady who could smell it.
Joy Milne, for the uninitiated: https://www.npr.org/sections/health-shots/2020/03/23/8202745...
"One possibility: a leading hypothesis pursued by researchers (and funders) was built on science that now appears to be fraudulent."
Possibly the most likely possibility?
There are multiple factors, but the one that contributes the most is that it's actually a very challenging disease to study and improve on.
1. It acts on the brain, one of the organs we understand the least.
2. It's relatively slow acting, and easy to miss in the early stages.
3. It impacts the older population which will have confounding health factors.
4. It doesn't fit neatly into a big category we already know a lot about, like infection or cancer.
Elaborating a bit - brain is hard to study since you can't easily take a biopsy of it (from a living person at least), and various brain scans are not great at identifying the stuff we care about.
The slow acting nature of it means also you have to wait a long time to see results of clinical trials; also because early stages are easy to miss that also means you are stuck studying people who are already pretty senile and thus might be beyond the point where you can make a big difference.
Ruxandra has a nice piece, focused on cancer, but the reasoning is basically the same here: biology is just really hard. Sometimes we get lucky but in general it's a long, slow slog.
[1] https://www.writingruxandrabio.com/p/why-havent-biologists-c...
You can't definitively diagnose it without an autopsy of the brain.
The science was delayed a decade due to fraud.
Not just a decade
Can u tell me what this is about?
I liked the story as told here in Science: https://www.science.org/content/article/potential-fabricatio...
The amyloid hypothesis and associated fraud covered in the TFA.
I'm not saying I'm the best informed on this topic, but I thought the root cause has been known for a long time now as degraded endocrine and cardiovascular function.
That's also why Alzheimer's can take so long to develop. It's just one aspect that we've chosen to focus on because it's more clearly noticeable, but it cannot easily be treated in isolation from everything else. If it was, it would regress quickly without fixing the root causes.
We truly do not know the root cause. There are plenty of folks with "degraded" endocrine, cardiovascular, and both systems. Most of them do not develop Alzheimer's.
There is no single root cause. Many scientists have preferred to ignore this fact and that has been a serious problem. Everyone likes a simple story. Age-related diseases are not simple stories.
We just keep forgetting about it!
...because Alzheimer is a dormant side effect of a virus, not of a messenger chemical. But that doesn't go well in studies and "self populism" of what funded research wanted to hear.
If you study effects and not causes due to lack of measurements for reproducibility in any field of research, that's what comes out.
Also check out how the correlation on how it started by observing the Wales eligibility for mandatory shingles vaccination during an outbreak and the effect on that test group when it comes to alzheimer or dementia in their old age.
Note that shingles (herpes zoster) virus is a dormant virus for decades, and it's not really treated because of that.
Also note that this was only discovered because people died and their data set was publicized because of that, which I hope that can happen in an anonymous way due to it being invaluable for medical research.
[1] https://www.alzheimer-europe.org/news/analysis-electronic-he...
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC11485228/
[3] https://www.sciencedirect.com/science/article/pii/S009286742...
[4] https://www.alzforum.org/news/research-news/shingles-vaccine...
Same scam and politics as the Ancel Keys lipid-heart hypothesis. Complete BS, ego and career protectionism, resulted in the deaths of millions and most people still believe that crap.
It is a "There is No Antimemetics Division" kind of scenario. They discover the cure and then keep forgetting it.
Its done substantially better than more common diseases like ME/CFS which very few have even heard of let alone know the symptoms of and receives almost no funding at all. Alzheimer's received a further $100 million of NIH funding earlier this year (https://www.alz.org/news/2026/100-million-dollar-alzheimers-...). That is 6 times the total funding for ME/CFS federally which is currently just 15 million and planned to decline.
The research went awry in Alziemer's due to fraud but its being funded at a reasonable level, a level many with Long Covid or ME/CFS or Fibromylgia would be very happy to see but doubt will ever happen. Funding of diseases is not "fair", it isn't based on number of sufferers * quality life years lost and we should be spending more on medical research generally. Alzeimers is one of the better funded diseases in the world.
No clue why you think chronic fatique syndrome and dementia ought to be treated as equally debilitating or serious by the medical community, but I'm sure you're the only person on this earth who holds that opinion.
Naturally, the far more terrifying and inexorable disease that is incurable and robs people of their entire personality and will affect most of us to some extent (dementia, if not Alzheimer's specifically) by the end of our lives gets more funding and attention, as it should. The way Alzheimer's has been researched and funded is diabolical, though, but you might pick any other of 200 serious progressive neurological disorders that are underfunded and underrepresented over... CFS. CFS isn't even fully accepted as a syndrome at this point - long COVID is probably more accepted as a real thing by practitioners at this point than CFS.
> long COVID is probably more accepted as a real thing by practitioners at this point than CFS
Isn't long covid just CFS that can be attributed to Covid?
If you accept that multiple viruses can cause "long <virus>" syndromes, of which long covid is just one example, it's plausible that CFS is really a cluster of syndromes, one category of which is these post viral syndromes. We just can't pinpoint the virus behind it every time because most viruses haven't been studied as much as Covid has.