The dendritic hypothesis for Alzheimer's disease pathophysiology

Brain Res Bull. 2014 Apr;103:18-28. doi: 10.1016/j.brainresbull.2013.12.004. Epub 2013 Dec 12.

Abstract

Converging evidence indicates that processes occurring in and around neuronal dendrites are central to the pathogenesis of Alzheimer's disease. These data support the concept of a "dendritic hypothesis" of AD, closely related to the existing synaptic hypothesis. Here we detail dendritic neuropathology in the disease and examine how Aβ, tau, and AD genetic risk factors affect dendritic structure and function. Finally, we consider potential mechanisms by which these key drivers could affect dendritic integrity and disease progression. These dendritic mechanisms serve as a framework for therapeutic target identification and for efforts to develop disease-modifying therapeutics for Alzheimer's disease.

Keywords: Amyloid; Calcium; Fyn; Postsynaptic; Spine; Tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Dendrites / physiology*
  • Dendrites / ultrastructure*
  • Humans
  • Neurites / ultrastructure
  • Tauopathies / pathology

Substances

  • Amyloid beta-Peptides