When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer's disease

Ageing Res Rev. 2014 Nov;18:29-40. doi: 10.1016/j.arr.2014.07.004. Epub 2014 Jul 28.

Abstract

A growing body of research suggests that astrocytes play roles as contributors to the pathophysiology of Alzheimer's disease (AD). Several lines of evidence propose that activated astrocytes produce and release proinflammatory molecules that may be critical for the generation of amyloid-β peptide (Aβ). However, accumulating evidence indicates that Aβ may activate astrocytes, which leads to an increase in cytokines that has been suggested to be a causative factor in the cognitive dysfunction of AD; thus, a vicious circle may be created. Intrinsic inflammatory mechanisms may provide a regulatory system that is capable of influencing the neuronal microenvironment that affects neuronal survival. In this article, we address the evidence surrounding the interactions of dysfunctional astrocytes with neighboring neurons that may initiate a cascade of events that culminates with neuronal injury and the expression of the hallmark lesions of AD. Comprehensive knowledge of the molecular mechanisms underlying the participation of astrocytes in neurodegeneration could aid the development of therapies to restore proper astrocyte function that can be used in AD patients to prevent or alleviate the progression of the disease in a more efficient and comprehensive manner.

Keywords: Alzheimer's disease; Amyloid β metabolism; Astrocytes; Cytokines; Neurodegeneration; Neuroinflammation.

Publication types

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

MeSH terms

  • Alzheimer Disease / immunology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Neurons / immunology
  • Neurons / metabolism*
  • Neurons / pathology
  • Paracrine Communication
  • Signal Transduction

Substances

  • Amyloid beta-Peptides
  • Inflammation Mediators