Much of health research is a search for simple, bio-molecular causes for our medical problems. These can result in pill-solutions. Diseases tend to be more complex, but Alzheimers seemed to work that way, until this summer when it turned out that the data supporting the simple theory was faked. Alzheimer’s is a devastating cognitive disease that is accompanied by a degenerating brain, with sticky, beta-amyloid plaques and tangles. About 16 years ago, this report, published in Nature seemed to show that a beta-amyloid, Aβ*56, caused the plaques and caused cognitive decline independent of any other Alzheimers indicators.
We were on the way to a cure, or so it seemed. Several studies by this group backed the initial results, and much of Alzheimer’s research was directed into an effort to fill in the story, and find ways to reduce the amount and bonding of this amyloid and others like it. Several other groups claimed they could not find the amyloid at all, or show that amyloids caused the symptoms described. But most negative results went unpublished. The theory was so satisfying, and the evidence from a few so strong, that the NIH poured billions into this approach, over $1B in this year alone. The FDA approved aducanumab, a drug from Biogen, on the assumption that it should work, even though it showed little to no benefit, and had some deadly side effects. Other firms followed, asking for approval of related anti-amyloid drugs that should work.
When news of the fraud came out, detected by Matthew Scragg and a few lone curmudgeons, stock prices plummeted in the drug companies. It now appears that the original work was made up, presented to journals and to the NIH using photoshopped images. For the group that did the fake work, it may mean jail time, for most other groups, the claim is that their work is still relevant. Doctors still prescribe the medications as they have nothing better to offer (Aducanumab therapy costs $50,000 per year). Maybe it’s time to start looking at alternative approaches and theories, sidelined over the last 16 years.
Some alternative theories posit that another molecule is responsible, particularly tau, associated with the tangles. Another sidelined theory is that amyloids are good. For example, that it’s the loss of soluble amyloids that causes Alzheimer’s. Alternately, that inflammation is the root cause, and that the amyloid plaques and tangles are a response to the inflammation, a bandage, perhaps. These theories could explain why the anti-amyloid drugs so often resulted in patient death.
It’s also possible that the inability of nerve cells to dispose of waste is the cause of AZ. In heathy people, waste is removed through acidic enzymes within lysosomes. Patients with decreased acid activity have a buildup of waste that includes amyloids. Perhaps the cure is to restore the acid enzymes.
My favorite theory is based on statistical data that shows that fat people are less likely to develop Alzheimers. This might lead to a junk-food cure. The fitness industry is very much against this theory–It’s debated here. They tend to support the inflammation model, claiming that diseases cause Alzheimer’s and cause patients to loose weight first. Could be. I note that Henry Kissinger is the only active politician of my era, the early 70s, still alive and writing intelligently.
Robert Buxbaum, November 17-19, 2022. I hope that Matthew Schragg comes out OK, by the way. Ben Franklin pointed out, that “No good deed goes unpunished.”