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Journal of Alzheimer's disease : JAD
Published

Sex differences on tau, astrocytic, and neurodegenerative plasma biomarkers

Authors

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

Abstract

J Alzheimers Dis. 2025 Mar 28:13872877251329468. doi: 10.1177/13872877251329468. Online ahead of print.

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-tau181), 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-tau181 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.

PMID:40151917 | DOI:10.1177/13872877251329468

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg