Therapeutics of Alzheimer's disease: Past, present and future

Neuropharmacology. 2014 Jan;76 Pt A:27-50. doi: 10.1016/j.neuropharm.2013.07.004. Epub 2013 Jul 25.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia worldwide. The etiology is multifactorial, and pathophysiology of the disease is complex. Data indicate an exponential rise in the number of cases of AD, emphasizing the need for developing an effective treatment. AD also imposes tremendous emotional and financial burden to the patient's family and community. The disease has been studied over a century, but acetylcholinesterase inhibitors and memantine are the only drugs currently approved for its management. These drugs provide symptomatic improvement alone but do less to modify the disease process. The extensive insight into the molecular and cellular pathomechanism in AD over the past few decades has provided us significant progress in the understanding of the disease. A number of novel strategies that seek to modify the disease process have been developed. The major developments in this direction are the amyloid and tau based therapeutics, which could hold the key to treatment of AD in the near future. Several putative drugs have been thoroughly investigated in preclinical studies, but many of them have failed to produce results in the clinical scenario; therefore it is only prudent that lessons be learnt from the past mistakes. The current rationales and targets evaluated for therapeutic benefit in AD are reviewed in this article. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

Keywords: Alzheimer's disease; Amyloid; Dementia; Neurofibrillary tangles; Neuropharmacology.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / drug effects
  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Humans
  • Mitochondria / drug effects
  • Models, Biological
  • Molecular Targeted Therapy / trends*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Synaptic Transmission / drug effects
  • tau Proteins / drug effects

Substances

  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • tau Proteins