Version history

{
  "pmid": "36747024",
  "doi": "10.1038/s41593-023-01257-z",
  "abstract": "1. Nat Neurosci. 2023 Mar;26(3):406-415. doi: 10.1038/s41593-023-01257-z. Epub\n2023  Feb 6.\n\nPerivascular cells induce microglial phagocytic states and synaptic engulfment \nvia SPP1 in mouse models of Alzheimer's disease.\n\nDe Schepper S(1), Ge JZ(1), Sierksma A(2)(3), Crowley G(1), Ferreira LSS(1), \nGarceau D(4), Toomey CE(5)(6), Sokolova D(1), Rueda-Carrasco J(1), Shin SH(7), \nKim JS(7), Childs T(1), Lashley T(5)(8), Burden JJ(9), Sasner M(4), Sala \nFrigerio C(1), Jung S(7), Hong S(10).\n\nAuthor information:\n(1)UK Dementia Research Institute, Institute of Neurology, University College \nLondon, London, UK.\n(2)VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium.\n(3)Leuven Brain Institute, KU Leuven, Leuven, Belgium.\n(4)The Jackson Laboratory, Bar Harbor, ME, USA.\n(5)The Queen Square Brain Bank for Neurological Disorders, Department of \nClinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, \nLondon, UK.\n(6)Department of Clinical and Movement Neuroscience, UCL Queen Square Institute \nof Neurology, London, UK.\n(7)Department of Immunology and Regenerative Biology (IRB), Weizmann Institute \nof Science, Rehovot, Israel.\n(8)Department of Neurodegenerative diseases, UCL Queen Square Institute of \nNeurology, London, UK.\n(9)Laboratory for Molecular Cell Biology, University College London, London, UK.\n(10)UK Dementia Research Institute, Institute of Neurology, University College \nLondon, London, UK. soyon.hong@ucl.ac.uk.\n\nErratum in\n    Nat Neurosci. 2026 Mar;29(3):759. doi: 10.1038/s41593-025-02197-6.\n\nAlzheimer's disease (AD) is characterized by synaptic loss, which can result \nfrom dysfunctional microglial phagocytosis and complement activation. However, \nwhat signals drive aberrant microglia-mediated engulfment of synapses in AD is \nunclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is \nupregulated predominantly by perivascular macrophages and, to a lesser extent, \nby perivascular fibroblasts. Perivascular SPP1 is required for microglia to \nengulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb \nin presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse \nmodels results in prevention of synaptic loss. Furthermore, single-cell RNA \nsequencing and putative cell-cell interaction analyses reveal that perivascular \nSPP1 induces microglial phagocytic states in the hippocampus of a mouse model of \nAD. Altogether, we suggest a functional role for SPP1 in perivascular \ncells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic \nengulfment in mouse models of AD.\n\n© 2023. The Author(s).\n\nDOI: 10.1038/s41593-023-01257-z\nPMCID: PMC9991912\nPMID: 36747024 [Indexed for MEDLINE]\n\nConflict of interest statement: The authors declare no competing interests.",
  "journal": "Nat Neurosci",
  "year": 2023,
  "authors": "De Schepper S, Ge JZ, Sierksma A, Crowley G, Ferreira LSS, Garceau D, Toomey CE, Sokolova D, Rueda-Carrasco J, Shin SH",
  "url": "https://pubmed.ncbi.nlm.nih.gov/36747024",
  "external_ids": {
    "doi": "10.1038/s41593-023-01257-z",
    "pmid": "36747024"
  },
  "citation_count": 2,
  "domain": "neurodegeneration"
}