학술논문
Plasma phosphorylated tau-217 exhibits sex-specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults.
Document Type
Academic Journal
Author
Saloner R; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; VandeVrede L; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Asken BM; Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, USA.; Paolillo EW; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Gontrum EQ; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Wolf A; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Lario-Lago A; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Milà-Alomà M; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.; Triana-Baltzer G; Neuroscience Biomarkers, Janssen Research & Development, LLC, San Diego, California, USA.; Kolb HC; Neuroscience Biomarkers, Janssen Research & Development, LLC, San Diego, California, USA.; Dubal DB; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Rabinovici GD; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.; Miller BL; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Boxer AL; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Casaletto KB; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.; Kramer JH; Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California, USA.
Source
Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: Accumulating 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.
Methods: We 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.
Results: In 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.
Discussion: Plasma 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.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Methods: We 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.
Results: In 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.
Discussion: Plasma 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.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)