{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:03:35Z","timestamp":1751515415474,"version":"3.41.0"},"posted":{"date-parts":[[2024,8,9]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,26]]},"abstract":"<title>Abstract<\/title>\n        <p>The canonical AD pathological cascade posits that the accumulation of amyloid beta (A\u03b2) is the initiating event, accelerating the accumulation of tau in the entorhinal cortex (EC), which subsequently spreads into the neocortex. Here in a sample of over 1300 participants with multimodal imaging and genetic information we queried how genetic variation affects these stages of the AD cascade. We observed that females and APOE-\u03b54 homozygotes are more susceptible to the effects of A\u03b2 on the primary accumulation of tau, with greater EC tau for a given level of A\u03b2. Furthermore, we observed for individuals who have rare risk variants in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) and\/or APOE-\u03b54 homozygotes there was a greater spread of primary tau from the EC into the neocortex. These findings offer insights into the function of sex, APOE and microglia in AD progression, and have implications for determining personalised treatment with drugs targeting A\u03b2 and tau.<\/p>","DOI":"10.21203\/rs.3.rs-4804430\/v1","type":"posted-content","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T13:56:16Z","timestamp":1723211776000},"source":"Crossref","is-referenced-by-count":1,"title":["Variable and interactive effects of Sex, APOE \u03b54 and TREM2 on the deposition of tau in entorhinal and neocortical regions."],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3704-5977","authenticated-orcid":false,"given":"Joseph","family":"Giorgio","sequence":"first","affiliation":[{"name":"University of California, Berkeley"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Jonson","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Statistics and Actuarial Science, The University of Iowa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-2634","authenticated-orcid":false,"given":"Jennifer","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"UCSF"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingshen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, University of California Berkeley"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-113X","authenticated-orcid":false,"given":"William","family":"Jagust","sequence":"additional","affiliation":[{"name":"University of California, Berkeley"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4804430\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4804430\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:15:48Z","timestamp":1751440548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4804430\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-4804430\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41467-025-60370-8","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,8,9]]},"subtype":"preprint"}}