In Defense Of The Amyloid Hypothesis

A guest post by David Schneider-Joseph The "amyloid hypothesis" says that Alzheimer's is caused by accumulation of the peptide amyloid-β. It's the leading model in academia, but a favorite target for science journalists, contrarian bloggers, and neuroscience public intellectuals, who point out problems like: Some of the research establishing amyloid's role turned out to be fraudulent. The level of amyloid in the brain doesn't correlate very well with the level of cognitive impairment across Alzheimer's patients. Several strains of mice that were genetically programmed to have extra amyloid did eventually develop cognitive impairments. But it took much higher amyloid levels than humans have, and on further investigation the impairments didn't really look like Alzheimer's. Some infectious agents, like the gingivitis bacterium and the herpesviruses, seem to play a role in at least some Alzheimer's cases. . . . and amyloid is one of the body's responses to injury or infection, so it might be a harmless byproduct of these infections or whatever else the real disease is. Anti-amyloid drugs (like Aduhelm) don't reverse the disease, and only slow progression a relatively small amount. Opponents call the amyloid hypothesis zombie science, propped up only by pharmaceutical companies hoping to sell off a few more anti-amyloid me-too drugs before it collapses. Meanwhile, mainstream scientists . . . continue to believe it without really offering any public defense. Scott was so surprised by the size of the gap between official and unofficial opinion that he asked if someone from the orthodox camp would speak out in its favor. I am David Schneider-Joseph, an engineer formerly with SpaceX and Google, now working in AI safety. Alzheimer's isn't my field, but I got very interested in it, spent six months studying the literature, and came away believing the amyloid hypothesis was basically completely solid. I thought I'd share that understanding with current skeptics. https://www.astralcodexten.com/p/in-defense-of-the-amyloid-hypothesis