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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 [beta]. 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 [mu]m) and performed correlations between both measures. As expected, both astrocytes and microglia were clearly spatially associated with ThioS-positive plaques (p = 0.0001, <=50 [mu]m vs >50 [mu]m 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 [beta]. By contrast, plaque-associated astrocytic response does not correlate with plaque size and seems to parallel the behavior of plaque-associated neuritic damage.

(C) 2013 by American Association of Neuropathologists, Inc.