Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies

Pharmacol Ther. 2019 Mar:195:186-198. doi: 10.1016/j.pharmthera.2018.11.006. Epub 2018 Nov 12.

Abstract

Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly population, is characterized by progressive cognitive decline and pathological hallmarks of amyloid plaques and neurofibrillary tangles. However, its pathophysiological mechanisms are poorly understood, and diagnostic tools and interventions are limited. Here, we review recent research on the amyloid hypothesis and beta-amyloid-induced dysfunction of neuronal synapses through distinct cell surface receptors. We also review how tau protein leads to synaptotoxicity through pathological modification, localization, and propagation. Finally, we discuss experimental therapeutics for AD and propose potential applications of disease-modifying strategies targeting synaptic failure for improved treatment of AD.

Keywords: Beta-amyloid; Excitotoxicity; Kinase; Receptor; Synaptic failure; Tau.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Cognition
  • Humans
  • Synapses / physiology*
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins