ArticleThe EMBO journal2023
Microglia-synapse engulfment via PtdSer-TREM2 ameliorates neuronal hyperactivity in Alzheimer's disease models.
Article in The EMBO journal, 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 81 papers.
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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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Who cites it
81 citing papers in PubMed, 103 citations in OpenAlex.
- Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-frontotemporal dementia.Acta neuropathologica · 2026Article
- Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model.Science advances · 2026Article
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Perisynaptic Astrocytic Processes as Communication Hubs and Early Sites of Dysfunction.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- Synaptic activity controls local exposure of an 'eat-me' signal via ANO3-ITPR1 signaling.bioRxiv : the preprint server for biology · 2026Article
- Disruption of the brain-spleen axis impairs monocyte-microglia communication and accelerates disease progression in a mouse model of amyloidosis.Nature communications · 2026Article
- Metabolic Brain Disorders: Prodromes, Symptoms, and Syndromes.International journal of molecular sciences · 2026Review
- Iba1 deficiency impairs microglial synaptic remodeling and neuronal survival after axonal injury.Journal of neuroinflammation · 2026Article
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- TREM2-mediated microglial phagocytosis of inhibitory synapses contributes to prolonged FS-induced epileptogenesis.Cell death discovery · 2026Article
- A scalable human-zebrafish xenotransplantation model reveals gastrosome-mediated processing of dying neurons by human microglia.Communications biology · 2026Article
- How Do Amyloid Pathology and Aberrant Neuronal Activity Disrupt Plasticity and Memory in Alzheimer's Disease?The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- 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
- Dual Role of Microglial TREM2 in Neuronal Degeneration and Regeneration After Axotomy.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- Dual association patterns between microglial activation and neuronal health in Alzheimer's disease: a whole-brain MRSI/PET study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- The glia-immune network: Astrocytes and oligodendrocytes as microglial co-ordinators in health and disease.The Journal of physiology · 2026Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Neuronal hyperactivity is a key feature of early stages of Alzheimer's disease (AD). Genetic studies in AD support that microglia act as potential cellular drivers of disease risk, but the molecular determinants of microglia-synapse engulfment associated with neuronal hyperactivity in AD are unclear. Here, using super-resolution microscopy, 3D-live imaging of co-cultures, and in vivo imaging of lipids in genetic models, we found that spines become hyperactive upon Aβ oligomer stimulation and externalize phosphatidylserine (ePtdSer), a canonical "eat-me" signal. These apoptotic-like spines are targeted by microglia for engulfment via TREM2 leading to amelioration of Aβ oligomer-induced synaptic hyperactivity. We also show the in vivo relevance of ePtdSer-TREM2 signaling in microglia-synapse engulfment in the hAPP NL-F knock-in mouse model of AD. Higher levels of apoptotic-like synapses in mice as well as humans that carry TREM2 loss-of-function variants were also observed. Our work supports that microglia remove hyperactive ePtdSer
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What OpenQuestion holds
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.