Here's hoping it pans out.

However, the skeptic in me remembers that the story about "plaques and tangles" being the cause/result of Alzheimer's didn't exactly pan out and seems to have been a 10+ year journey down the wrong path (to put things too crudely). Science.org on the faked beta amyloid data (from July 2022):

[...]

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 AB*56 oligomer itself (I’ll be glad to be corrected on this point, though). What there have been are trials that (to a greater or lesser extent) tried to target the whole amyloid-oligomer hypothesis in general, but I have to think that those would have happened anyway. In case you’re wondering, Biogen’s recent aducanumab antibody seems to hit both aggregated amyloid in plaques and some types of oligomers, not that it mattered in the end. The idea of amyloid oligomers as a key driver of AD is not a crazy one in any way, and people were going to put it to the test whether the *56 paper came out or not.

Most of these have been antibodies, as that last link shows. A non-antibody approach is ALZ-801, which is the small molecule homotaurine and is claimed to inhibit amyloid oligomer formation in general. The problem is that this drug has already failed an Alzheimer’s Phase III, and I’m not convinced by the attempts at post-hoc analysis being done to revive its prospects. But antibody or small molecule, though, nothing has worked.

All this said, the excitement over the AB*56 work surely did accelerate things. We probably got more clinical trials, sooner, than we would have otherwise. Perhaps in a way this might have helped to bury the hypothesis even more quickly than otherwise? There's no way of knowing.

What Now?

Well, as the world well knows, every single Alzheimer’s trial to date has failed. I know, I know, there are all sorts of special pleadings for aducanumab and what have you, if you look at the data sideways with binoculars you can start to begin to see the outlines of the beginnings of efficacy, sure, sure. I’m not having it. 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.

[...]

The Brain Research paper unsurprisingly - it's only been out a few weeks - hasn't been cited yet. It will be interesting to see if this result holds up and can be extended.

Thanks again.

Cheers,
Scott.