ArticleNature neuroscience2023
Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease.
Article in Nature neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 201 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
201 citing papers in PubMed, 3 syntheses or guidelines pooled it, 261 citations in OpenAlex.
- Improving reproducibility of differentially expressed genes in single-cell transcriptomic studies of neurodegenerative diseases through meta-analysis.Nature communications · 2025Pooled it
- Osteopontin in Alzheimer's Disease: A Double-Edged Sword in Neurodegeneration and Neuroprotection-A Systematic Review.CNS neuroscience & therapeutics · 2025Pooled it
- Cerebrospinal fluid inflammatory biomarkers for disease progression in Alzheimer's disease and multiple sclerosis: a systematic review.Frontiers in immunology · 2023Pooled it
- TXNRD1-driven enteric glial remodeling promotes neuronal dysfunction in Hirschsprung disease.iScience · 2026Article
- Maresin1 Improves Angiogenesis and Cognitive Function by Regulating Perivascular Macrophages in Rats with Chronic Cerebral Hypoperfusion.Neurochemical research · 2026Article
- Article
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Transcriptomic Signatures of Microglial Phagocytosis Reveal Diagnostic Markers and Immune Landscape in Alzheimer's Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- NOTCH-mediated glial CXCL9:SPP1 polarization by GSK3β exacerbates postnatal enteric nervous system dysfunction in Hirschsprung disease.Journal of gastroenterology · 2026Article
- Isoform Remodeling and Promoter Switching Identify Altered Transcriptional Regulation in Alzheimer's Disease Frontal Cortex.Research square · 2026Article
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.Nature genetics · 2026Article
- Neuron-derived SPP1 instructs microglia to limit degeneration.Science advances · 2026Article
- Review
- Driving tumor-associated macrophages to a CXCL9Cell reports. Medicine · 2026Article
- Deep Plasma Proteomics-Based Diagnostic Panel for Early Detection of Amnestic Mild Cognitive Impairment.Journal of proteome research · 2026Article
- Choroid plexus inflammation in bipolar disorder.Brain, behavior, and immunity · 2026Article
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- Targeting SPP1 requires moving beyond ligand blockade.Cellular & molecular immunology · 2026Article
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 4 institutions in 4 countries.
Funding
Abstract
Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts. Perivascular SPP1 is required for microglia to engulf synapses and upregulate phagocytic markers including C1qa, Grn and Ctsb in presence of amyloid-β oligomers. Absence of Spp1 expression in AD mouse models results in prevention of synaptic loss. Furthermore, single-cell RNA sequencing and putative cell-cell interaction analyses reveal that perivascular SPP1 induces microglial phagocytic states in the hippocampus of a mouse model of AD. Altogether, we suggest a functional role for SPP1 in perivascular cells-to-microglia crosstalk, whereby SPP1 modulates microglia-mediated synaptic engulfment in mouse models of AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.