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

ACS Chem Neurosci. 2017 Jul 19;8(7):1435-1437. doi: 10.1021/acschemneuro.7b00188. Epub 2017 Jun 6.

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 Aβ 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.

Keywords: Alzheimer’s disease; Amyloid-β; computer simulations; drugs; in vitro and in vivo studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Drug Discovery
  • Humans
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use*

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents