阿米洛イド假说认为阿尔茨海默症由β-淀粉样蛋白肽的积累引起，是学术界的主流模型。尽管该假说面临争议，如部分研究被指造假、脑内淀粉样蛋白水平与认知障碍程度不匹配、小鼠实验所需淀粉样蛋白水平远高于人类等，但主流科学家仍支持它。本文作者David Schneider-Joseph通过研究文献，坚定地认为阿米洛イド假说是基本正确的，旨在回应科学界的质疑。

🔬 阿米洛イド假说认为阿尔茨海默症由β-淀粉样蛋白肽的积累引起，是学术界的主流模型。该假说基于多项研究，但部分研究被发现存在造假问题，影响了其可信度。

🐭 动物实验显示，小鼠需要远高于人类的淀粉样蛋白水平才会出现认知障碍，且这些障碍与阿尔茨海默症的症状不完全一致，表明该假说在人类身上的适用性存疑。

🤝 尽管存在争议，主流科学家仍支持阿米洛イド假说，而科学记者、博主和公众知识分子则经常质疑其有效性，认为它可能被制药公司利用来推广抗淀粉样蛋白药物。

🔬 作者David Schneider-Joseph通过深入研究文献，认为阿米洛イド假说是基本正确的，旨在为该假说提供支持，回应科学界的质疑和批评。

🤝 尽管阿米洛イド假说面临争议，但它仍然是研究阿尔茨海默症的重要方向，未来可能需要更多研究来验证或修正该假说。

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