Sex differences on tau, astrocytic, and neurodegenerative plasma biomarkers

Background Sex 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. Objective The 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. Methods Plasma 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 181 ), and total tau (t-tau). Baseline and longitudinal analyses evaluated for any significant associations between sex and AD-related plasma biomarkers. Results Females 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 181 or t-tau. Conclusions This 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.