{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lall D"],"funding":["NIA NIH HHS","Howard Hughes Medical Institute","NINDS NIH HHS"],"pagination":["2275-2291.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8298293"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["109(14)"],"pubmed_abstract":["C9orf72 repeat expansions cause inherited amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and result in both loss of C9orf72 protein expression and production of potentially toxic RNA and dipeptide repeat proteins. In addition to ALS/FTD, C9orf72 repeat expansions have been reported in a broad array of neurodegenerative syndromes, including Alzheimer's disease. Here we show that C9orf72 deficiency promotes a change in the homeostatic signature in microglia and a transition to an inflammatory state characterized by an enhanced type I IFN signature. Furthermore, C9orf72-depleted microglia trigger age-dependent neuronal defects, in particular enhanced cortical synaptic pruning, leading to altered learning and memory behaviors in mice. Interestingly, C9orf72-deficient microgl"],"journal":["Neuron"],"pubmed_title":["C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation."],"pmcid":["PMC8298293"],"funding_grant_id":["R01 AG056303","R01 NS085207","R01 NS090934","P30 AG066519","RF1 AG055524","R01 NS097545","RF1 NS090934","UE5 NS065723","R25 NS065723","R01 AG061895","P50 AG016573","R01 AG047644","K08 NS105916","RF1 AG047644"],"pubmed_authors":["Lall D","Landeros J","Mota TA","Mahan TE","Shelest O","Blurton-Jones M","Holtzman DM","Ulrich JD","Kim J","Rexach JE","Lorenzini I","Vazquez M","Baloh RH","Davtyan H","O'Rourke JG","Sattler R","Bell S","Ghaffari L","Muhammad AKMG","Geschwind DH"],"additional_accession":[]},"is_claimable":false,"name":"C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation.","description":"C9orf72 repeat expansions cause inherited amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and result in both loss of C9orf72 protein expression and production of potentially toxic RNA and dipeptide repeat proteins. In addition to ALS/FTD, C9orf72 repeat expansions have been reported in a broad array of neurodegenerative syndromes, including Alzheimer's disease. Here we show that C9orf72 deficiency promotes a change in the homeostatic signature in microglia and a transition to an inflammatory state characterized by an enhanced type I IFN signature. Furthermore, C9orf72-depleted microglia trigger age-dependent neuronal defects, in particular enhanced cortical synaptic pruning, leading to altered learning and memory behaviors in mice. Interestingly, C9orf72-deficient microgl","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2026-05-09T03:09:21.856Z","creation":"2025-02-18T23:32:06.002Z"},"accession":"S-EPMC8298293","cross_references":{"pubmed":["34133945"],"doi":["10.1016/j.neuron.2021.05.020"]}}