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However, sex differences in plasma phosphorylated tau (p\u2010tau)217 prediction of subclinical cognitive and brain changes are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We measured baseline plasma p\u2010tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) in 163 participants (85 cognitively unimpaired [CU], 78 mild cognitive impairment [MCI]). In CU, linear mixed effects models examined sex differences in plasma biomarker prediction of longitudinal domain\u2010specific cognitive decline and brain atrophy. Cognitive models were repeated in MCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In CU females, baseline plasma p\u2010tau217 predicted verbal memory and medial temporal lobe trajectories such that trajectories significantly declined once p\u2010tau217 concentrations surpassed 0.053 pg\/ml, a threshold that corresponded to early levels of cortical amyloid aggregation in secondary amyloid positron emission tomography analyses. CU males exhibited similar rates of cognitive decline and brain atrophy, but these trajectories were not dependent on plasma p\u2010tau217. Plasma GFAP and NfL exhibited similar female\u2010specific prediction of medial temporal lobe atrophy in CU. Plasma p\u2010tau217 exhibited comparable prediction of cognitive decline across sex in MCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Plasma p\u2010tau217 may capture earlier Alzheimer's disease (AD)\u2010related cognitive and brain atrophy hallmarks in females compared to males, possibly reflective of increased susceptibility to AD pathophysiology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13454","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T13:45:46Z","timestamp":1693230346000},"page":"376-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Plasma phosphorylated tau\u2010217 exhibits sex\u2010specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired 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