Once upon a time, the Amyloid Cascade Hypothesis

Ageing Res Rev. 2024 Jan:93:102161. doi: 10.1016/j.arr.2023.102161. Epub 2023 Dec 6.

Abstract

Recent trials with monoclonal antibodies targeting amyloid-β (Aβ) in Alzheimer's disease (AD) have sparked a renewed interest in disease-modifying therapies. Despite their promise, these trials leave the issue open and posit some doubts about the validity of the Amyloid Cascade Hypothesis (ACH). While some scores of neurocognitive tests improved upon treatment, real-world clinical benefits were minimal. This Viewpoint discusses additional, often overlooked findings from these trials. We also emphasize the multifactorial nature of AD and the need for a broader research perspective beyond the simplistic disease model provided by the ACH.

Keywords: Aducanumab; Alzheimer's disease; Dementia; Donanemab; Lecanemab; Neurodegeneration.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / therapy
  • Amyloid
  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Antibodies, Monoclonal
  • Humans

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Amyloidogenic Proteins
  • Antibodies, Monoclonal