Sex Differences on Tau, Astrocytic and Neurodegeneration Plasma Biomarkers

Abstract

AbstractBackgroundSex differences have consistently been identified on autopsy, neuroimaging, and cerebrospinal fluid outcomes related to Alzheimer’s disease (AD). 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. 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.MethodsThe sample included 567 participants (248 males, 319 females) from the Boston University AD Research Center (BUADRC). Participants completed a battery of neuropsychological tests. Cognitive diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. All participants had at least one blood draw between 2008 and 2018 at the BUADRC. Plasma samples were analyzed using Simoa for phosphorylated tau (p‐tau181), total tau (t‐tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). Linear regression models tested associations between sex and each plasma biomarker, controlling for age, racial identity, education, and APOE ε4 carrier status. Analyses were repeated stratified by APOE ε4 carrier and CDR status.Results Table 1 shows sample characteristics (mean age = 74.41, 13.3% Black/African American). As shown in Table 2, the multivariable linear regressions showed significant sex effects for plasma GFAP, such that females had higher plasma GFAP levels than males (p<.001). Among APOE ε4 carriers (n = 223) and participants with a CDR≥1 (n = 111), the associations with GFAP remained and the magnitude of associations were stronger compared to APOE ε4 non‐carriers and those with a CDR<1. Figure 1 shows plots of the association between sex and each plasma biomarker. There were no other sex effects across the other plasma biomarkers in the entire sample or when stratified by APOE ε4 carrier or CDR status.ConclusionsFemales had higher plasma GFAP levels than males regardless of APOE ε4 status and cognitive status. Reactive astrocyte processes associated with neurodegenerative diseases can be measured by plasma GFAP. Biological differences in these processes may explain observed associations between sex and risk for AD. The study highlights the dynamic utility of plasma biomarkers for the study of AD and longitudinal analyses of this cohort are planned.