{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Danhash EP"],"funding":["NCATS NIH HHS","Edward N. and Della L. Thome Memorial Foundation","NIA NIH HHS","National Institutes of Health","Hope Center for Neurological Disorders","Chan Zuckerberg Initiative","NIH HHS","National Institute on Aging","Washington University","The recruitment and clinical characterization of Knight"],"pagination":["e70580"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371455"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(8)"],"pubmed_abstract":["<h4>Introduction</h4>Genome-wide association studies have identified MS4A4A, a microglia-enriched gene, as a modulator of Alzheimer's disease (AD) risk. Common variants in MS4A4A affect AD susceptibility, gene expression, triggering receptor expressed on myeloid cells 2 (TREM2) signaling, and microglial transcriptional states, but the gene's functional role remains unclear.<h4>Methods</h4>Using a novel model, we investigated the impact of Ms4a4a loss in the 5xFAD mouse model of amyloid beta (Aβ) accumulation.<h4>Results</h4>Ms4a4a deficiency reduced steady-state Aβ levels and shortened its half-life in brain interstitial fluid. Aged 5xFAD mice lacking Ms4a4a exhibited more compact plaques and lower overall plaque burden. Microglia deficient in Ms4a4a showed a pro-inflammatory profile and e"],"journal":["Alzheimer's & dementia : the journal of the Alzheimer's Association"],"pubmed_title":["Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation."],"pmcid":["PMC12371455"],"funding_grant_id":["UL1 TR002345","P30 AG066444","P30AG066444","P01 AG026276","P01AG026276","R01 AG062734","RF1 AG058501","P01AG03991","AG058501","AG062734","P01 AG003991","R01 AG058501"],"pubmed_authors":["Miller N","Nadarajah CJ","You SF","Verbeck AC","Huang G","Starr E","Iyer AK","Tiemann Powles S","Western D","Herz J","Danhash EP","Cruchaga C","Musiek ES","Karch CM","Diaz-Pacheco AS","Galasso G","Cirrito J"],"additional_accession":[]},"is_claimable":false,"name":"Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation.","description":"<h4>Introduction</h4>Genome-wide association studies have identified MS4A4A, a microglia-enriched gene, as a modulator of Alzheimer's disease (AD) risk. Common variants in MS4A4A affect AD susceptibility, gene expression, triggering receptor expressed on myeloid cells 2 (TREM2) signaling, and microglial transcriptional states, but the gene's functional role remains unclear.<h4>Methods</h4>Using a novel model, we investigated the impact of Ms4a4a loss in the 5xFAD mouse model of amyloid beta (Aβ) accumulation.<h4>Results</h4>Ms4a4a deficiency reduced steady-state Aβ levels and shortened its half-life in brain interstitial fluid. Aged 5xFAD mice lacking Ms4a4a exhibited more compact plaques and lower overall plaque burden. Microglia deficient in Ms4a4a showed a pro-inflammatory profile and e","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-07-15T14:23:59.048Z","creation":"2026-07-05T03:12:07.03Z"},"accession":"S-EPMC12371455","cross_references":{"pubmed":["40843775"],"doi":["10.1002/alz.70580"]}}