Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease

Rona Baron, Alicia A Babcock, Anna Nemirovsky, Bente Finsen, Alon Monsonego

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Abstrakt

    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 Alzheimer'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 Alzheimer'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.

    OriginalsprogEngelsk
    TidsskriftAging Cell
    Vol/bind13
    Udgave nummer4
    Sider (fra-til)584-595
    ISSN1474-9718
    DOI
    StatusUdgivet - 2014

    Fingeraftryk

    Dyk ned i forskningsemnerne om 'Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease'. Sammen danner de et unikt fingeraftryk.

    Citationsformater