Sex differences on tau, astrocytic, and neurodegenerative plasma biomarkers

BackgroundSex differences have consistently been identified on autopsy, neuroimaging, and cerebrospinal fluid outcomes related to Alzheimer's disease (AD), but the exact mechanisms for these associations are unclear. Blood-based biomarkers are practical alternatives for the investigation of mechanisms of AD, in addition to accurate disease detection and monitoring.ObjectiveThe objective of this study was to examine sex differences across a panel of blood-based plasma biomarkers in participants with and without cognitive impairment due to AD.MethodsPlasma samples were collected from 567 participants from across the AD diagnostic continuum (i.e., normal cognition (NC), mild cognitive impairment (MCI), and dementia) and analyzed for glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau at threonine 181 (p-tau<sub>181</sub>), and total tau (t-tau). Baseline and longitudinal analyses evaluated for any significant associations between sex and AD-related plasma biomarkers.ResultsFemales were found to have higher plasma GFAP compared to males at baseline regardless of cognitive diagnosis. Among those with AD dementia, females were also found to have higher NfL levels compared to males. Longitudinal analyses found that higher plasma NfL at baseline was associated with an increased risk of worsening AD dementia status only in females. No significant findings were observed for p-tau<sub>181</sub> or t-tau.ConclusionsThis study found significant sex differences in plasma biomarkers of GFAP and NfL. Further research is needed to better understand the underlying mechanisms mediating these differences.

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Publication Details

Journal
Journal of Alzheimer s Disease
Published
2025-03-28
DOI
https://doi.org/10.1177/13872877251329468
Citations
8
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
11.77

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article

Sex differences on tau, astrocytic, and neurodegenerative plasma biomarkers

Rhoda Au, Joseph Palmisano, Thor D. Stein, Gyungah Jun et al.
8 citations
Journal of Alzheimer s Disease
Dementia and Cognitive Impairment Research
11.77
article

Sex differences on tau, astrocytic, and neurodegenerative plasma biomarkers

Rhoda Au, Joseph Palmisano, Thor D. Stein, Gyungah Jun, Ann Carolyn McKee, Andrew E. Budson, Lindsay A. Farrer, Lee E. Goldstein, Hugo J. Aparicio, Wei Qiao Qiu, Brett Martin, Thomas K. Karikari, Eric G Steinberg, Michael L. Alosco, Katherine W. Turk, Maureen K. O’Connor, Robert A. Stern, Brandon Frank, Michael A. Sugarman, Kaj Blennow, Henrik Zetterberg, Yorghos Tripodis, Irene Simkin, Jesse Mez, Erika Pettway, Nicholas J. Ashton, Sarah J. Banks, Jacob Labonte
article en
8 citations

Abstract

BackgroundSex differences have consistently been identified on autopsy, neuroimaging, and cerebrospinal fluid outcomes related to Alzheimer's disease (AD), but the exact mechanisms for these associations are unclear. Blood-based biomarkers are practical alternatives for the investigation of mechanisms of AD, in addition to accurate disease detection and monitoring.ObjectiveThe objective of this study was to examine sex differences across a panel of blood-based plasma biomarkers in participants with and without cognitive impairment due to AD.MethodsPlasma samples were collected from 567 participants from across the AD diagnostic continuum (i.e., normal cognition (NC), mild cognitive impairment (MCI), and dementia) and analyzed for glial fibrillary acidic protein (GFAP), neurofilament light (NfL), phosphorylated tau at threonine 181 (p-tau<sub>181</sub>), and total tau (t-tau). Baseline and longitudinal analyses evaluated for any significant associations between sex and AD-related plasma biomarkers.ResultsFemales were found to have higher plasma GFAP compared to males at baseline regardless of cognitive diagnosis. Among those with AD dementia, females were also found to have higher NfL levels compared to males. Longitudinal analyses found that higher plasma NfL at baseline was associated with an increased risk of worsening AD dementia status only in females. No significant findings were observed for p-tau<sub>181</sub> or t-tau.ConclusionsThis study found significant sex differences in plasma biomarkers of GFAP and NfL. Further research is needed to better understand the underlying mechanisms mediating these differences.

Journal of Alzheimer s DiseaseVol. 105(2)
Boston University (US), University of Science and Technology of China (CN), University of Wisconsin–Madison (US), Medical University of South Carolina (US), University of Pittsburgh (US), King's College London (GB), Stavanger University Hospital (NO), Edith Nourse Rogers Memorial Veterans Hospital (US), Sahlgrenska University Hospital (SE), VA Boston Healthcare System (US), Centre for Mental Health (GB), University of California San Diego (US), Sorbonne Université (FR), VA New England Healthcare System (US), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), Institut du Cerveau (FR), University College London (GB), University of Gothenburg (SE)
Clinical and Translational Science Institute, Boston University, National Institute on Aging
Good health and well-being
Openalex Percentile: Top 1%
Dementia and Cognitive Impairment Research
11.77
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