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Immunology of neurodegenerative diseases

Perivascular signals drive microglial appetite

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Microglial synapse engulfment precedes brain amyloid plaque formation and probably contributes to early cognitive decline in Alzheimer’s disease. The mechanisms that regulate microglia-mediated synapse engulfment are unclear. De Schepper et al. show that perivascular SPP1 induces microglia-mediated synapse engulfment, highlighting a neuroimmune interaction that contributes to synapse loss in amyloid pathology.

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Fig. 1: SPP1 release from perivascular cells induces microglial phagocytosis of synapses at early stages of amyloid pathology in a mouse model of AD.

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Authors and Affiliations

  1. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Carleigh A. O’Brien & F. Chris Bennett

  2. Division of Neurology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    F. Chris Bennett

Authors
  1. Carleigh A. O’Brien
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  2. F. Chris Bennett
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Correspondence to F. Chris Bennett.

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The authors declare no competing interests.

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O’Brien, C.A., Bennett, F.C. Perivascular signals drive microglial appetite. Nat Neurosci 26, 369–370 (2023). https://doi.org/10.1038/s41593-023-01256-0

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