The amyloid fraud controversy -- what it is and what it isn't

Since the news broke that some of what we thought we understood about the role of beta amyloid in Alzheimer's disease may have been based on fraudulent work, the scandal has spread widely in the media.  I've read a number of articles about it, and they have often misunderstood the significance of the event.  And so, a couple of points:

-- The amyloid hypothesis is not fundamentally based on the fraudulent research.  Discarding the research does not simply negate subsequent research and clinical trials based on the hypothesis. 

-- Discarding the apparently fraudulent research does create an awkward situation for the amyloid hypothesis.  Failures of clinical trials for treatments such as Aduhelm and BAN2401 will be looked at under an entirely different light. 

-- The research purported to have identified a unique species of beta amyloid, Aβ*56, that might have had a special role in Alzheimer's disease.  But, with or without Aβ*56, amyloid plaques do form in the brains of people with Alzheimer's disease, and they have some role in the disease.  Treatments like Aduhelm and BAN2401 do remove the plaques.

Nevertheless, so much research has been based on the assumption that Aβ*56 exists and plays a role in the development of Alzheimer's disease, researchers now feel much less confident in many of the treatments under development.  Our greatest faith has been placed on the proposition that monoclonal antibodies eating up amyloid plaques will alter the progression of the disease, and this is the basis for these treatments.  So there is anxiety that our most promising treatments have been barking up a wrong tree.

In Beating the Dementia Monster, we cautiously expressed skepticism about the amyloid hypothesis.  The illusion of Aβ*56 may explain why Aduhelm struggled so hard to demonstrate effectiveness.  I'm thinking the members of the FDA's advisory panel who quit when Aduhelm was approved are likely feeling very vindicated right now.

In Beating the Dementia Monster, we cited several other hypotheses that deserve attention from researchers.  An outspoken amyloid skeptic wrote this long but excellent article on the controversy.  In fact, it's the best writing I've seen since this terrible news broke.  One point he makes -- a very important point -- is that interest in the amyloid hypothesis supported by the belief in Aβ*56 has distracted researchers from pursuing other avenues that might have produced better results for those suffering from the disease and their families. 

And, as we did in our last post, he quotes Harvard's Dennis Selkoe in saying, "I hope that people will not become faint-hearted as a result of what really looks like a very egregious example of malfeasance that’s squarely in the Aβ oligomer field. But if current phase 3 clinical trials of three drugs targeting amyloid oligomers all fail, the Aβ hypothesis is very much under duress.”