{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T13:14:57Z","timestamp":1793279697510,"version":"4.5.0"},"reference-count":65,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"741","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,4,3]]},"abstract":"<jats:p>\n                    Microglia help limit the progression of Alzheimer\u2019s disease (AD) by constraining amyloid-\u03b2 (A\u03b2) pathology, effected through a balance of activating and inhibitory intracellular signals delivered by distinct cell surface receptors. Human leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory receptor of the immunoglobulin (Ig) superfamily that is expressed on myeloid cells and recognizes apolipoprotein E (ApoE) among other ligands. Here, we find that LILRB4 is highly expressed in the microglia of patients with AD. Using mice that accumulate A\u03b2 and carry a transgene encompassing a portion of the\n                    <jats:italic>LILR<\/jats:italic>\n                    region that includes\n                    <jats:italic>LILRB4<\/jats:italic>\n                    , we corroborated abundant LILRB4 expression in microglia wrapping around A\u03b2 plaques. Systemic treatment of these mice with an anti-human LILRB4 monoclonal antibody (mAb) reduced A\u03b2 load, mitigated some A\u03b2-related behavioral abnormalities, enhanced microglia activity, and attenuated expression of interferon-induced genes. In vitro binding experiments established that human LILRB4 binds both human and mouse ApoE and that anti-human LILRB4 mAb blocks such interaction. In silico modeling, biochemical, and mutagenesis analyses identified a loop between the two extracellular Ig domains of LILRB4 required for interaction with mouse ApoE and further indicated that anti-LILRB4 mAb may block LILRB4-mApoE by directly binding this loop. Thus, targeting LILRB4 may be a potential therapeutic avenue for AD.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adj9052","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T13:58:22Z","timestamp":1712152702000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":45,"title":["Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3829-7551","authenticated-orcid":true,"given":"Jinchao","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO 63110, 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