{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:08:52Z","timestamp":1785431332905,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,4]]},"group-title":"Neuroscience","reference-count":28,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["RF1AG058852"],"award-info":[{"award-number":["RF1AG058852"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F30AG074618"],"award-info":[{"award-number":["F30AG074618"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["DVT-14-321148"],"award-info":[{"award-number":["DVT-14-321148"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  While genetics implicate a central role for dysregulated innate immunity in Alzheimer\u2019s disease (AD), the contributions of peripheral myeloid cells, such as monocytes, have been largely overlooked in favor of microglia. Here, we investigate whether AD associated loci, specifically\n                  <jats:italic>rs3865444<\/jats:italic>\n                  in the\n                  <jats:italic>CD33<\/jats:italic>\n                  locus and\n                  <jats:italic>rs1057233<\/jats:italic>\n                  in the\n                  <jats:italic>SPI1<\/jats:italic>\n                  locus, converge on shared functional pathways in monocytes in the context of amyloid-beta peptide 1-42 (A\u03b21-42) as an immune stimulus. To do so, we isolated monocytes from peripheral blood mononuclear cells (PBMCs) from healthy individuals and exposed them to aggregated A\u03b21-42. In this study, we identify functional convergence of the\n                  <jats:italic>CD33<\/jats:italic>\n                  and\n                  <jats:italic>SPI1<\/jats:italic>\n                  AD risk variants in the context of aggregated A\u03b2, both resulting in reduced phagocytosis and loss of surface TREM2 expression, demonstrating an interaction between genetics and environment to reduce myeloid cell fitness. These findings highlight that peripheral monocytes, like brain-resident microglia, are genetically and functionally linked to AD risk, underscoring their importance as accessible immune cells that contribute to disease susceptibility and progression.\n                <\/jats:p>","DOI":"10.1101\/2025.11.02.686117","type":"posted-content","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T13:55:24Z","timestamp":1762264524000},"source":"Crossref","is-referenced-by-count":0,"title":["Alzheimer\u2019s Disease Risk Variants Interact with Amyloid-beta to Modulate Monocyte Function"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-6305","authenticated-orcid":false,"given":"Zena K.","family":"Chatila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-4325","authenticated-orcid":false,"given":"Elizabeth 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