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Functional impairment of microglia coincides with beta-amyloid deposition in mice with Alzheimer-like pathology

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Item Type:Article
Title:Functional impairment of microglia coincides with beta-amyloid deposition in mice with Alzheimer-like pathology
Creators Name:Krabbe, G. and Halle, A. and Matyash, V. and Rinnenthal, J.L. and Eom, G.D. and Bernhardt, U. and Miller, K.R. and Prokop, S. and Kettenmann, H. and Heppner, F.L.
Abstract:Microglial cells closely interact with senile plaques in Alzheimer's disease and acquire the morphological appearance of an activated phenotype. The significance of this microglial phenotype and the impact of microglia for disease progression have remained controversial. To uncover and characterize putative changes in the functionality of microglia during Alzheimer's disease, we directly assessed microglial behavior in two mouse models of Alzheimer's disease. Using in vivo two-photon microscopy and acute brain slice preparations, we found that important microglial functions - directed process motility and phagocytic activity - were strongly impaired in mice with Alzheimer's disease-like pathology compared to age-matched non-transgenic animals. Notably, impairment of microglial function temporally and spatially correlated with A{beta} plaque deposition, and phagocytic capacity of microglia could be restored by interventionally decreasing amyloid burden by A{beta} vaccination. These data suggest that major microglial functions progressively decline in Alzheimer's disease with the appearance of A{beta} plaques, and that this functional impairment is reversible by lowering A{beta} burden, e.g. by means of A{beta} vaccination.
Keywords:Alzheimer Disease, Amyloid beta-Peptides, Amyloid Plaque, Animal Disease Models, Cell Movement, Microglia, Mutation, Phagocytosis, Protein Multimerization, Secondary Protein Structure, Spatio-Temporal Analysis, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e60921
Date:8 April 2013
Official Publication:https://doi.org/10.1371/journal.pone.0060921
PubMed:View item in PubMed

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