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Why has there been so little progress on Alzheimer's disease?

https://freakonomics.com/podcast/why-has-there-been-so-little-progress-on-alzheimers-disease/
61•chiefalchemist•1h ago

Comments

robwwilliams•1h ago
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.

saghm•1h ago
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.
robwwilliams•47m ago
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.
hx8•30m ago
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.

SOLAR_FIELDS•33m ago
Reminds me of schizophrenia. A hodgepodge of different things lumped into a single label of "broad class of things we don't understand"
readthenotes1•1h ago
"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?

hx8•33m ago
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.

levocardia•15m ago
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...

hcknwscommenter•14m ago
You can't definitively diagnose it without an autopsy of the brain.
PaulKeeble•1h ago
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.

avazhi•49m ago
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.

klipt•37m ago
> 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.

jmward01•44m ago
'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.
omeysalvi•44m ago
It is a "There is No Antimemetics Division" kind of scenario. They discover the cure and then keep forgetting it.
sublinear•40m ago
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.

hcknwscommenter•16m ago
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.
tim-tday•38m ago
The science was delayed a decade due to fraud.
onesandofgrain•36m ago
Can u tell me what this is about?
buescher•22m ago
The amyloid hypothesis and associated fraud covered in the TFA.
dillydogg•8m ago
I liked the story as told here in Science: https://www.science.org/content/article/potential-fabricatio...
ekianjo•30m ago
Not just a decade
panabee•38m ago
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.

manquer•27m ago
> 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.

panabee•8m ago
If you're a wealthy person lacking a neurobiology background, how do you decide which research efforts are "prudent" to support? 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.

ki4jgt•26m ago
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.

beaned•15m ago
I'm surprised that better science never resulted from that lady who could smell it.

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