{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:12:45Z","timestamp":1791886365214,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012541","name":"Guangdong Innovative and Entrepreneurial Research Team Program","doi-asserted-by":"publisher","award":["2021ZT09Y104"],"award-info":[{"award-number":["2021ZT09Y104"]}],"id":[{"id":"10.13039\/100012541","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer's Disease (AD) is a neurodegenerative condition characterized by the accumulation and deposition of amyloid\u2010\u03b2 (A\u03b2) aggregates in the brain. Despite a wealth of research on the toxicity of A\u03b2 and its role in synaptic damage, the mechanisms facilitating A\u03b2 clearance are not yet fully understood. However, microglia, the primary immune cells of the central nervous system, are known to maintain homeostasis through the phagocytic clearance of protein aggregates and cellular debris. In this study, RNA sequencing analysis and live cell functional screens are employed to uncover microglial genetic modifiers related to AD.\n                    <jats:italic>Lyzl4<\/jats:italic>\n                    is identified, which encodes a c\u2010type lysozyme\u2010like enzyme primarily localized to microglial lysosomes, as a gene significantly upregulated in AD microglia with aging and propose that\n                    <jats:italic>Lyzl4<\/jats:italic>\n                    upregulation acts as a positive regulator of A\u03b2 clearance. Furthermore, it is found that\n                    <jats:italic>Lyzl4<\/jats:italic>\n                    overexpression boosts A\u03b2 clearance both in vitro and in vivo, underscoring its potential for mitigating A\u03b2 burden. These novel insights position\n                    <jats:italic>Lyzl4<\/jats:italic>\n                    as a promising therapeutic target for Alzheimer's disease, paving the way for further exploration into potential AD treatments.\n                  <\/jats:p>","DOI":"10.1002\/advs.202412184","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T06:59:41Z","timestamp":1731913181000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Microglial Lyzl4 Facilitates \u03b2\u2010Amyloid Clearance in Alzheimer's Disease"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1973-8019","authenticated-orcid":false,"given":"Jie","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pathology Stanford University School of Medicine  Palo Alto CA 94305 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