ArticleNeuron2017
TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss.
Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 1 of them a synthesis that pooled it.
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Who cites it
138 citing papers in PubMed, 1 synthesis or guideline pooled it, 255 citations in OpenAlex.
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- TMEM106B is a selective modulator of TDP-43 pathology in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Riluzole shifts glial responses to protect synapses and memory in Aβ oligomer-treated rats.Journal of neuroinflammation · 2026Article
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- Redox regulation of neuroinflammatory pathways contributes to damage in Alzheimer's disease brain.Cell chemical biology · 2026Article
- Protease-Mediated TAR DNA-Binding Protein 43 (TDP-43) Pathogenesis: From Molecular Mechanisms to Therapeutic Opportunities.ACS pharmacology & translational science · 2026Review
- Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice.Nature neuroscience · 2026Article
- TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.The Journal of clinical investigation · 2026Article
- TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.EMBO molecular medicine · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Sleep rescues age-associated loss of glial engulfment.PLoS genetics · 2026Article
- Enhancer RNA-mediated transcriptional regulation of TDP-43 during early neural lineage specification.Animal cells and systems · 2026Article
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.Research square · 2025Article
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.bioRxiv : the preprint server for biology · 2025Article
- ALS/FTD-linked TBK1 deficiency in microglia induces an aged-like microglial signature and drives social recognition deficits in mice.Nature communications · 2025Article
- From Amyloid to Synaptic Dysfunction: Biomarker-Driven Insights into Alzheimer's Disease.Current issues in molecular biology · 2025Review
- Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.Molecular neurodegeneration · 2025Review
- Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- Early-life adversities compromise behavioral development in male and female mice heterozygous for CNTNAP2.Neurobiology of stress · 2025Article
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
78 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Microglia coordinate various functions in the central nervous system ranging from removing synaptic connections, to maintaining brain homeostasis by monitoring neuronal function, and clearing protein aggregates across the lifespan. Here we investigated whether increased microglial phagocytic activity that clears amyloid can also cause pathological synapse loss. We identified TDP-43, a DNA-RNA binding protein encoded by the Tardbp gene, as a strong regulator of microglial phagocytosis. Mice lacking TDP-43 in microglia exhibit reduced amyloid load in a model of Alzheimer's disease (AD) but at the same time display drastic synapse loss, even in the absence of amyloid. Clinical examination from TDP-43 pathology cases reveal a considerably reduced prevalence of AD and decreased amyloid pathology compared to age-matched healthy controls, confirming our experimental results. Overall, our data suggest that dysfunctional microglia might play a causative role in the pathogenesis of neurodegenerative disorders, critically modulating the early stages of cognitive decline.
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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.