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Nintil - The failure of monoclonal antibody therapy for Alzheimer's Disease, implications for the Amyloid Cascade Hypothesis

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In a previous post I explained the basics of Alzheimer's disease and the current state of the art in our understanding of it. I focused on the amyloid-tau story while hinting at the fact that there are other factors worth exploring. I mentioned the "repeated failures of Alzheimer's drugs in the clinic". This post is about that. I mostly focused on the Aducanumab case, with solanezumab and lecanemab as contrasts. These trials have been used as evidence against the amyloid cascade hypothesis (ACH). After reviewing them I do not think these refute the ACH, but they strongly speak against a naive model where amyloid removal at any stage of the disease will stop progression. Aducanumab/Aduhelm is a monoclonal antibody against amyloid that was controversially approved by the FDA despite their Peripheral and Central Nervous System Drugs Advisory Committee recommending not approving it (None of the 11 members recommended approving it) . Some of them even resigned over the FDA's decision. Many

Table of Contents Aducanumab Solanezumab: This happened before Lecanemab: Is there any hope? All the trials, everywhere, all at once Primary prevention of Alzheimer's Analysis of clinical trial data should not engage in naive frequentism Does this falsify the Amyloid Cascade Hypothesis? Changelog In a previous post I explained the basics of Alzheimer's disease and the current state of the art in our understanding of it. I focused on the amyloid-tau story while hinting at the fact that there are other factors worth exploring. I mentioned the "repeated failures of Alzheimer's drugs in the clinic

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