title: Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease.
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.
authors: Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Massachusetts Alzheimer Disease Research Center, and Harvard Medical School, Charlestown, Massachusetts, USA.
authors: Alberto
authors: A
authors: Serrano-Pozo
authors: Alona
authors: A
authors: Muzikansky
authors: Teresa
authors: T
authors: Gómez-Isla
authors: John H
authors: JH
authors: Growdon
authors: Rebecca A
authors: RA
authors: Betensky
authors: Matthew P
authors: MP
authors: Frosch
authors: Bradley T
authors: BT
authors: Hyman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology*
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