Progress in Alzheimer's disease drug discovery: an update

Curr Opin Investig Drugs. 2009 Jan;10(1):23-34.


While Alzheimer's disease (AD) represents a major healthcare challenge, with 25 to 34 million individuals currently affected worldwide and triple this number of patients projected by 2050, the drugs currently approved for the palliative treatment of AD, the cholinesterase inhibitors and the NMDA antagonist memantine, have demonstrated questionable efficacy, highlighting an urgent need for new therapies. Efforts in targeting the removal of amyloid plaques from the brain of patients with AD have been disappointing, with neither plaque-removing vaccines nor the gamma-secretase modulator, tarenflurbil demonstrating clinical benefit, thus questioning the validity of the amyloid cascade hypothesis that has driven AD research for the past decade. The lack of progress in mechanistic approaches (the amyloid and tau hypotheses) to developing new AD drugs indicates that some of the basic assumptions of AD causality and the search for effective drugs are probably in need of major reassessment and redirection.

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amyloid / metabolism
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Drug Design*
  • Drug Industry*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Molecular Structure
  • tau Proteins / metabolism


  • Amyloid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Indoles
  • tau Proteins
  • Amyloid Precursor Protein Secretases
  • latrepirdine