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Six genes (n\n                      <jats:sub>genes<\/jats:sub>\n                      (%); 2(33%) X\u2010linked) interacted with A\u03b2\u2010PET, whereas 103 genes (3(3%) X\u2010linked) interacted with neocortical tau\u2010PET, to influence cognitive decline. A total of 110 genes (17(15%) X\u2010linked) and 3156 genes (121(4%) X\u2010linked) were moderated by both sex and A\u03b2\u2010 or tau\u2010PET, respectively. Pathway enrichment analyses reflected immunity, protein synthesis, and lipid metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings underscore the importance of peripheral transcriptomic markers in identifying sex\u2010differentiated pathways related to risk of and protection from cognitive decline in preclinical AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71225","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T03:18:11Z","timestamp":1771816691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole blood gene expression moderates associations between AD biomarkers and cognitive decline in cognitively unimpaired older adults"],"prefix":"10.1002","volume":"22","author":[{"given":"Hannah M.","family":"Klinger","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mabel","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Alzheimer's Research and Treatment Brigham and Women's Hospital and Harvard Medical School, Boston  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav A.","family":"Janve","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory &amp; Alzheimer's Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Clifton","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory &amp; Alzheimer's Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Birkenbihl","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian T.","family":"Coughlan","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana L.","family":"Townsend","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Properzi","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Zyski","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory &amp; Alzheimer's Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory &amp; Alzheimer's Center Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca E.","family":"Amariglio","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's Research and Treatment Brigham and Women's Hospital and Harvard Medical School, Boston  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn V.","family":"Papp","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's Research and Treatment Brigham and Women's Hospital and Harvard Medical School, Boston  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorene M.","family":"Rentz","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's Research and Treatment Brigham and Women's Hospital and Harvard Medical School, Boston  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Sik","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Alzheimer's Research and Treatment Brigham and Women's Hospital and Harvard Medical School, Boston  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmeer","family":"Chhatwal","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Donohue","sequence":"additional","affiliation":[{"name":"Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rema","family":"Raman","sequence":"additional","affiliation":[{"name":"Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Rissman","sequence":"additional","affiliation":[{"name":"Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Aisen","sequence":"additional","affiliation":[{"name":"Alzheimer's Therapeutic Research Institute University of Southern California  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa A.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Alzheimer's Research and Treatment Brigham and Women's Hospital and Harvard Medical School, Boston  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory &amp; 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