Wikipedia is correct to say it's widely believed that plaques cause Alzheimer's, because the new evidence is still encountering resistance. The hallmark of science is falsification. We now have many drugs that remove amyloid plaques with few side effects. Removing plaques does not improve symptoms or halt progression [1, 2].
Furthermore, 60% people over 80 have these plaques but only 10% develop dementia [3].
Ergo, the hypothesis that plaques cause of Alzheimer's is pretty much falsified. More than likely they may be a biomarker of some kind that may be associated with cognitive decline of some sort.
I can't get the whole paper, but your first link seems to be saying that we've put all our eggs into one basket and we are ignoring too many other theories. It doesn't go so far as to say the amyloid angle is bunk, does it?
Your second link says this:
> researchers have said experimental treatments targeting the beta amyloid protein might not have worked in the past because the doses were too low or the patient populations used for the trials should have been younger
Again, that doesn't seem to be concluding the amyloid & tau street is a dead end.
The Alzheimer's Association site (alz.org) agrees:
> Alzheimer's has no cure, but one treatment — aducanumab (Aduhelm™) — is the first therapy to demonstrate that removing amyloid, one of the hallmarks of Alzheimer’s disease, from the brain is reasonably likely to reduce cognitive and functional decline in people living with early Alzheimer’s.
> I can't get the whole paper, but your first link seems to be saying that we've put all our eggs into one basket and we are ignoring too many other theories. It doesn't go so far as to say the amyloid angle is bunk, does it?
> Furthermore, the blind adherence to the “Amyloid code” [297] has resulted in the overwhelming rationalization of clinical trial failures - the lack of validation of the amyloid hypothesis – as being due to recurring issues in their planning and execution, not that the hypothesis has failed in its validation. This viewpoint, described as “sheer obstinacy in the face of compelling proof ..[of being]… on the wrong track” [285] has also compromised the translational approach to AD therapeutics making the criteria for compound advancement from preclinical research to the clinic exclusively based on either a blind faith in a hypothesis or animal models that have proven irrelevant.
This addresses the special pleading you quoted from people who continue trying to explain away the failures of the amyloid model.
The writing is on the wall, but as they say, "science advances one funeral at a time".
Furthermore, 60% people over 80 have these plaques but only 10% develop dementia [3].
Ergo, the hypothesis that plaques cause of Alzheimer's is pretty much falsified. More than likely they may be a biomarker of some kind that may be associated with cognitive decline of some sort.
[1] https://pubmed.ncbi.nlm.nih.gov/30273552/
[2] https://www.advisory.com/daily-briefing/2020/02/12/alzheimer...
[3] https://nutritionreview.org/2021/07/amyloid-plaques-are-cons...