Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease

Aging Cell. 2014 Aug;13(4):584-95. doi: 10.1111/acel.12210. Epub 2014 Mar 18.


Microglia integrate within the neural tissue with a distinct ramified morphology through which they scan the surrounding neuronal network. Here, we used a digital tool for the quantitative morphometric characterization of fine cortical microglial structures in mice, and the changes they undergo with aging and in Alzheimer's-like disease. We show that, compared with microglia in young mice, microglia in old mice are less ramified and possess fewer branches and fine processes along with a slightly increased proinflammatory cytokine expression. A similar microglial pathology appeared 6-12 months earlier in mouse models of Alzheimer's disease (AD), along with a significant increase in brain parenchyma lacking coverage by microglial processes. We further demonstrate that microglia near amyloid plaques acquire unique activated phenotypes with impaired process complexity. We thus show that along with a chronic proinflammatory reaction in the brain, aging causes a significant reduction in the capacity of microglia to scan their environment. This type of pathology is markedly accelerated in mouse models of AD, resulting in a severe microglial process deficiency, and possibly contributing to enhanced cognitive decline.

Keywords: Alzheimer's disease; aging; amyloid beta-peptide; inflammation; microglia; morphology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Antigens, CD / metabolism
  • Apyrase / metabolism
  • CD11b Antigen / metabolism
  • Cell Shape
  • Cerebral Cortex / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Green Fluorescent Proteins / metabolism
  • Inflammation Mediators / metabolism
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Microglia / pathology*
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology*


  • Amyloid beta-Peptides
  • Antigens, CD
  • CD11b Antigen
  • Cytokines
  • Inflammation Mediators
  • Green Fluorescent Proteins
  • Leukocyte Common Antigens
  • Apyrase
  • CD39 antigen