Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift

Neuron. 2011 Jan 27;69(2):203-13. doi: 10.1016/j.neuron.2011.01.002.

Abstract

Most current Alzheimer's disease (AD) therapies in advanced phases of development target amyloid β-peptide (Aβ) production, aggregation, or accumulation. Translational models suggest that anti-Aβ therapies may be highly effective if tested as agents to prevent or delay development of the disease or as therapies for asymptomatic patients with very early signs of AD pathology. However, anti-Aβ therapeutics are currently being tested in symptomatic patients where they are likely to be much less effective or ineffective. The lack of alignment between human clinical studies and preclinical studies, together with predictions about optimal trial design based on our understanding of the initiating role of Aβ aggregates in AD, has created a treatment versus prevention dilemma. In this perspective, we discuss why it is imperative to resolve this dilemma and suggest ways for moving forward in the hopes of enhancing the development of truly effective AD therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Apolipoprotein E4 / genetics
  • Apolipoprotein E4 / metabolism
  • Biomarkers / metabolism
  • Clinical Trials as Topic
  • Disease Progression
  • Health Services Needs and Demand
  • Humans
  • Translational Medical Research

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers