Open AccessAccelerated microglial pathology is associated with A β plaques in mouse models of A lzheimer's disease
Author(s) -
Baron Rona,
Babcock Alicia A.,
Nemirovsky Anna,
Finsen Bente,
Monsonego Alon
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12210
Subject(s) - microglia , proinflammatory cytokine , parenchyma , biology , neuroscience , neuroinflammation , pathology , phenotype , alzheimer's disease , cognitive decline , immunology , disease , inflammation , medicine , dementia , biochemistry , gene
Summary 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 A lzheimer'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 A lzheimer'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.