This discussion about the cause of Alzheimer's is not new, it has been going on for something like 10-15 years at least. What is triggering the publicity now is that two drugs targeting amyloid failed to produce real improvement even though they were effective at reducing amyloid. Especially the newer one produced very large and measurable reduction of amyloid, but only very small (but measurable) cognitive improvement.

In any case the whole amyloid system is involved somehow, I think that much is very likely. Just not in the way that the visible amyloid fibers are the cause, but might just be another symptom. This is not anything like heretical talk, this suspicion was pretty much mainstream when I studied biochemistry ~15 years ago. It was only a hypothesis, but it certainly wasn't suppressed.

I thought the promising results of lecanemab were supportive of the amyloid hypothesis.

You'd think that after a decade of failed results, someone would go back to the drawing board and start again. But it never seems to happen.

We have only recently had any drugs that could reduce the beta amyloid. While they do reduce the amyloid, they do not see to have an equivalent impact on the actual disease. That failure IS prompting people to reconsider other root causes, again.

Welcome to market driven science.

This is driven by grant writing. That’s the literal opposite of market driven

It’s the market of grant-funding agencies.

that's true for any sociopolitical system, and the reason why i push back on dichotomous thinking, especially "left-right" or "democrat-republican" in political discussions. this is the central exploration of Wisdom of Crowds, which i recommend to everyone even though it's considered 'old' now.

> the same dangerous theme keeps surfacing: dangerous theme keeps surfacing: monolithic thinking, with “no alternatives allowed”

That might be part of it. I think a bigger part is, "we don't know what X is so we can't measure it, but Y seems to coincide with X and we can measure Y, so let's focus on Y".

This probably happens a lot and sometimes it works out, but it also often doesn't. It failed with dietary cholesterol, and Alzheimer's is the just the latest big failure of this approach.

I think unjustified "monolithic thinking" in this instance was bad. I'd say that's because in medicine, so many maladies are multifactorial and thus one shouldn't declare victory till your model shows strong effectiveness in the field.

But "monolithic thinking" is also accepting established theory. Unlimited diversity can open the door to all sorts of crap - I don't want "diversity" in whether a doctor accepts the germ theory of (some) disease, the existence of viruses, etc.