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

Authors

  • Rona Baron,

    1. The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Alicia A. Babcock,

    1. Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
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  • Anna Nemirovsky,

    1. The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Bente Finsen,

    1. Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
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  • Alon Monsonego

    Corresponding author
    1. The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel
    • Correspondence

      Professor Alon Monsonego, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Tel.: 972 86479052; fax: 972 86479051;

      e-mail: alonmon@exchange.bgu.ac.il

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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 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.

Ancillary