> But my impression is that a lot of labs that were interested in the general idea of beta-amyloid oligomers just took the earlier papers as validation for that interest, and kept on doing their own research into the area without really jumping directly onto the 56 story itself. The bewildering nature of the amyloid-oligomer situation in live cells has given everyone plenty of opportunities for that! The expressions in the literature about the failure to find 56 (as in the Selkoe lab’s papers) did not de-validate the general idea for anyone - indeed, Selkoe’s lab has been working on amyloid oligomers the whole time and continues to do so. Just not Lesné’s oligomer.
And
> Did the 56 Work Lead to Clinical Trials? That’s a question that many have been asking since this scandal broke a few days ago. And the answer is that no, I have been unable to find a clinical trial that specifically targeted the AB56 oligomer itself (I’ll be glad to be corrected on this point, though).
> Every single disease-modifying trial of Alzheimer’s has failed.
> The huge majority of those have addressed the amyloid hypothesis, of course, from all sorts of angles. Even the truest believers are starting to wonder. Dennis Selkoe’s entire career has been devoted to the subject, and he’s quoted in the Science article as saying that if the trials that are already in progress also fail, then “the A-beta hypothesis is very much under duress”. Yep.
And the original expose is quite interesting if you haven't read it yet https://www.science.org/content/article/potential-fabricatio...
However, the particular faked data, despite lots of citations, has apparently not lead to any clinical trials:
> Did the AB*56 Work Lead to Clinical Trials? That’s a question that many have been asking since this scandal broke a few days ago. And the answer is that no, I have been unable to find a clinical trial that specifically targeted the AB*56 oligomer itself (I’ll be glad to be corrected on this point, though).
Marc Tessier-Lavigne https://stanforddaily.com/2023/02/17/internal-review-found-f...
Berislav Zlokovic https://www.science.org/content/article/misconduct-concerns-...
Hoau-Yan Wang https://www.science.org/content/article/co-developer-cassava...
Sylvain Lesné - the researcher from grandparent comment's article
This list taken from Chris Said on Twitter https://x.com/chris_said/status/1724448550493315436?s=46
The problem is viewing individual papers as the unit of truth in science. The "self-correcting" nature of science will actually reject entire papers, and entire directions of inquiry. Including, maybe, a casual relationship between beta amyloid and AD, but maybe not.
The other key part of science is holding everything in a state of uncertainty. There's some "facts" but mostly just hints and clues. And with Alzheimer's disease in particular we are trying to make progress with completely inadequate vision; we really can't even measure so much of what we want to measure. Feynman said it back in the 1960s, too, physicists have failed to deliver the tools to biologists to really measure what needs to be measured. There have been advancements, and DNA sequencing technology in the past decade has been turned into the most clever sorts of information theoretic microscopy by combining DNA sequences with many other biochemical processes. But we as a species still can not measure a lot of the things we'd like to measure.