Plasma phosphorylated tau‐217 exhibits sex‐specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults

Author:

Saloner Rowan1ORCID,VandeVrede Lawren1,Asken Breton M.2,Paolillo Emily W.1,Gontrum Eva Q.1,Wolf Amy1,Lario‐Lago Argentina1,Milà‐Alomà Marta3,Triana‐Baltzer Gallen4,Kolb Hartmuth C.4,Dubal Dena B.1,Rabinovici Gil D.13,Miller Bruce L.1,Boxer Adam L.1,Casaletto Kaitlin B.1,Kramer Joel H.1

Affiliation:

1. Department of Neurology Weill Institute for Neurosciences University of California, San Francisco San Francisco California USA

2. Department of Clinical and Health Psychology University of Florida Gainesville Florida USA

3. Department of Radiology and Biomedical Imaging University of California, San Francisco San Francisco California USA

4. Neuroscience Biomarkers Janssen Research & Development, LLC San Diego California USA

Abstract

AbstractINTRODUCTIONAccumulating evidence indicates disproportionate tau burden and tau‐related clinical progression in females. However, sex differences in plasma phosphorylated tau (p‐tau)217 prediction of subclinical cognitive and brain changes are unknown.METHODSWe measured baseline plasma p‐tau217, 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‐specific cognitive decline and brain atrophy. Cognitive models were repeated in MCI.RESULTSIn CU females, baseline plasma p‐tau217 predicted verbal memory and medial temporal lobe trajectories such that trajectories significantly declined once p‐tau217 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‐tau217. Plasma GFAP and NfL exhibited similar female‐specific prediction of medial temporal lobe atrophy in CU. Plasma p‐tau217 exhibited comparable prediction of cognitive decline across sex in MCI.DISCUSSIONPlasma p‐tau217 may capture earlier Alzheimer's disease (AD)‐related cognitive and brain atrophy hallmarks in females compared to males, possibly reflective of increased susceptibility to AD pathophysiology.

Funder

Larry L. Hillblom Foundation

Alzheimer's Association

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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