reviewBrainMay 15, 2023BRONZE OA

The amyloid cascade hypothesis: an updated critical review

Technical University of Denmark · Mount Sinai Medical Center · +7 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and have been heralded as corroboration of the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging and biochemical data suggest a more complex aetiology. Here we review the history and weaknesses of the amyloid cascade hypothesis in view of the new evidence obtained from clinical trials of anti-amyloid antibodies. These trials indicate that the treatments have either no or uncertain clinical effect on cognition. Despite the importance of amyloid in the definition of Alzheimer's disease, we argue that the data point to Aβ playing a minor…

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