ArticleCell reports. Medicine2023
Human astrocytes and microglia show augmented ingestion of synapses in Alzheimer's disease via MFG-E8.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 79 citations in OpenAlex.
- Clusterin is enriched in plaque-associated astrocytes and localizes to synapses in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-frontotemporal dementia.Acta neuropathologica · 2026Article
- Early Retinal UCHL1 Dysregulation Coupled With Synaptic Loss Reflects Alzheimer's Disease Severity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Microglial maturation across human and mouse as a reference for interpreting large-animal models of perinatal brain injury.Pediatric research · 2026Review
- Perisynaptic Astrocytic Processes as Communication Hubs and Early Sites of Dysfunction.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Article
- Differential selectivity of microglia and astrocytes in HIV-1 gp120-induced synaptic pruning.Brain : a journal of neurology · 2026Article
- Microglial Activation Under Hypoxic Conditions in Early Alzheimer's Disease: Can Natural SIRT1 Activators Be Therapeutic Allies in the Inflammation-Energy Axis?Phytotherapy research : PTR · 2026Review
- Microglia-Mediated Dysfunction of PKCγ Interneurons Underlies the Mechanical Hypersensitivity in Autism.Molecular neurobiology · 2026Article
- TLR7-induced murine inflammation results in a global neuroinflammatory response driving neural circuit-specific transcriptomic changes.Scientific reports · 2026Article
- Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease.The European journal of neuroscience · 2026Article
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peripheral Inflammatory Networks.Cellular and molecular neurobiology · 2026Review
- Cell type transcriptomic modules reveal shared molecular mechanisms in Alzheimer's and Parkinson's disease.GigaScience · 2026Article
- Exercise-induced modulation of astrocyte in Alzheimer's disease: mechanisms and therapeutic implications.Frontiers in physiology · 2026Review
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Astrocytic SIRT1 ameliorates cognitive deficits after traumatic brain injury via autophagy-mediated MEGF10 phagocytosis.Journal of neuroinflammation · 2025Article
- Sex-Specific Molecular Architecture of Microglia-Mediated Neuronal Pruning Across the Human Lifespan.Molecular neurobiology · 2025Article
- The mCells · 2025Review
Corrections and comments
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Authors and funding
27 authors at 7 institutions in 2 countries.
Funding
Abstract
Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence for any glial involvement in synapse removal in human AD remains to be established. Here we observe astrocytes and microglia from human brains contain greater amounts of synaptic protein in AD compared with non-disease controls, and that proximity to amyloid-β plaques and the APOE4 risk gene exacerbate this effect. In culture, mouse and human astrocytes and primary mouse and human microglia phagocytose AD patient-derived synapses more than synapses from controls. Inhibiting interactions of MFG-E8 rescues the elevated engulfment of AD synapses by astrocytes and microglia without affecting control synapse uptake. Thus, AD promotes increased synapse ingestion by human glial cells at least in part via an MFG-E8 opsonophagocytic mechanism with potential for targeted therapeutic manipulation.
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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.