Why Is Research on Amyloid-ß Failing to Give New Drugs for Alzheimer’s Disease?

Research output: Contribution to journalArticle

  • External authors:
  • Maria Del Castillo Frias
  • Olivia Berthoumieu
  • Bogdan Tarus
  • Jessica Nasica-Labouze
  • Fabio Sterpone
  • Phuong H Nguyen
  • Nigel M Hooper
  • Peter Faller
  • Philippe Derreumaux

Abstract

The two hallmarks of Alzheimer’s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting A have failed. From a review of the recent literature, and our own experience based on in vitro, in silico and in vivo studies, we present some reasons to explain this repetitive failure.

Bibliographical metadata

Original languageEnglish
JournalACS Chemical Neuroscience
Early online date6 Jun 2017
StateE-pub ahead of print - 6 Jun 2017