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It is determined that deletion of\n                    <jats:italic>Ms4a4a<\/jats:italic>\n                    , an AD\u2010associated gene, exacerbates seizures in amyloid \u03b2 (A\u03b2)\u2010driven AD mouse model.\n                    <jats:italic>MS4A4A<\/jats:italic>\n                    is significantly upregulated in brain lesions in patients with epilepsy. Single\u2010cell sequencing reveals that\n                    <jats:italic>MS4A4A<\/jats:italic>\n                    is highly expressed in microglia within these lesions, linked to enhanced phagocytic activity. Mechanistic investigation delineates that deletion of\n                    <jats:italic>Ms4a4a<\/jats:italic>\n                    impairs microglial phagocytosis, accompanied by diminished calcium influx and disruptions in mitochondrial metabolic fitness. The cytosolic fragment of\n                    <jats:italic>Ms4a4a<\/jats:italic>\n                    is anchored to the cytoskeletal components, supporting its critical role in mediating phagocytosis. Induction of\n                    <jats:italic>Ms4a4a<\/jats:italic>\n                    through central delivery of LNP\u2010\n                    <jats:italic>Il4<\/jats:italic>\n                    alleviates seizure conditions. Collectively, these findings identify\n                    <jats:italic>Ms4a4a<\/jats:italic>\n                    as a potential therapeutic target for managing seizures in AD treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202417733","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T06:59:56Z","timestamp":1746946796000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Microglial MS4A4A Protects against Epileptic Seizures in Alzheimer's Disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Meng","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute for Immunology and School of Basic Medical Sciences and Beijing Key Laboratory of Immunological Research of Allergy (LIRA) Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Basic Medical Sciences and Beijing Key Laboratory of Immunological Research of Allergy (LIRA) Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Basic Medical Sciences and Beijing Key Laboratory of Immunological Research of Allergy (LIRA) Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruochong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[{"name":"ENO Bio mRNA Innovation Institute Shenzhen Rhegen Biotechnology Co. 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Ltd  Shenzhen 518000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Cai","sequence":"additional","affiliation":[{"name":"Pediatric Epilepsy Center Peking University First Hospital  Beijing 100034 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoguo","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Pediatric Epilepsy Center Peking University First Hospital  Beijing 100034 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