Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in alzheimer disease

Alberto Serrano-Pozo, Alona Muzikansky, Teresa Gómez-Isla, John H. Growdon, Rebecca A. Betensky, Matthew P. Frosch, Bradley T. Hyman

Research output: Contribution to journalArticle

Abstract

Although it is clear that astrocytes and microglia cluster around dense-core amyloid plaques in Alzheimer disease (AD), whether they are primarily attracted to amyloid deposits or are just reacting to plaque-associated neuritic damage remains elusive. We postulate that astrocytes and microglia may differentially respond to fibrillar amyloid β. Therefore, we quantified the size distribution of dense-core thioflavin-S (ThioS)-positive plaques in the temporal neocortex of 40 AD patients and the microglial and astrocyte responses in their vicinity (≤50 μm) and performed correlations between both measures. As expected, both astrocytes and microglia were clearly spatially associated with ThioS-positive plaques (p = 0.0001, ≤50 μm vs >50 μm from their edge), but their relationship to ThioS-positive plaque size differed: larger ThioS-positive plaques were associated with more surrounding activated microglia (p = 0.0026), but this effect was not observed with reactive astrocytes. Microglial response to dense-core plaques seems to be proportional to their size, which we postulate reflects a chemotactic effect of amyloid β. By contrast, plaque-associated astrocytic response does not correlate with plaque size and seems to parallel the behavior of plaque-associated neuritic damage.

Original languageEnglish (US)
Pages (from-to)462-471
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Alzheimer disease
  • Amyloid plaques
  • Apolipoprotein E
  • Astrocytes
  • Microglia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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