Developing new treatments for Alzheimer's disease: the who, what, when, and how of biomarker-guided therapies

Int Psychogeriatr. 2008 Oct;20(5):871-89. doi: 10.1017/S1041610208007382. Epub 2008 May 23.

Abstract

This synthetic review presents an approach to the use of biomarkers for the development of new treatments for Alzheimer's disease (AD). After reviewing the process of translation as applied to AD, the paper provides a general update on what is known about the biology of the disease, and highlights currently available treatments. This is followed by a discussion of future drug development for AD emphasizing the roles that biomarkers are likely to play in this process: (1) define patients who are going to progress rapidly for the purpose of trial enrichment; (2) differentiate disease and therapeutically relevant AD subtypes; (3) assess the potential activity of specific therapies in vivo or ex vivo; and (4) measure the underlying disease state, so as to (a) detect disease and assess drug response in asymptomatic patients, (b) serve as a secondary outcome measure in clinical trials of symptomatic patients, and (c) decide if further development of a treatment should be stopped if not likely to be effective. Several examples are used to illustrate each biomarker utility in the AD context.

Publication types

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

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Aniline Compounds
  • Biomarkers / analysis*
  • Biomarkers, Pharmacological / analysis
  • Brain / pathology
  • Cholinesterase Inhibitors / therapeutic use
  • Clinical Trials as Topic
  • Cognition Disorders / diagnosis
  • Cognition Disorders / pathology
  • Cognition Disorders / therapy
  • Disease Progression
  • Drug Design
  • Humans
  • Neuropsychological Tests
  • Plaque, Amyloid / diagnostic imaging
  • Plaque, Amyloid / pathology
  • Positron-Emission Tomography / methods
  • Psychotropic Drugs / therapeutic use
  • Radioligand Assay
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Biomarkers
  • Biomarkers, Pharmacological
  • Cholinesterase Inhibitors
  • Psychotropic Drugs
  • Thiazoles