Presenter of 2 Presentations
SEX AFFECTS THE ASSOCIATION OF PLASMA GFAP WITH ALZHEIMER’S DISEASE PATHOPHYSIOLOGY
Abstract
Aims
Growing evidence suggests an increased age-independent prevalence of Alzheimer's disease (AD) in females compared to males. Elucidating how disease biomarkers correlate in females and males is critical to understanding the basis of sex differences in AD. Our aim was to evaluate sex-related differences in the association of plasma Glial fibrillary acidic protein (GFAP) levels, a biomarker of astrocyte reactivity, and Alzheimer's disease (AD) pathophysiology.
Methods
We cross-sectionally assessed participants from TRIAD cohorts. Unpaired t-test compare the difference in plasma GFAP levels between females and males. We performed linear regressions with an interaction term for sex to compare the associations of plasma GFAP with global Aβ PET load, cerebrovascular disease measured with white matter hyperintensity (WMH) , and neurodegeneration measured with hippocampal volume (HCV) between cognitively impaired females and males.
Results
We assessed 308 participants (MCI = 63 , AD =45 CN=200, mean age=69.8 (8) ). Females showed significantly higher GFAP levels than males (Fig 1). We found significant interaction terms and strong correlations between plasma GFAP levels and AD pathophysiology (Aβ PET) in females (R-squared=0.2; P=0.03) but not in males. Similarly, plasma GFAP was associated with vascular disease (WMH) (R-squared=0.3; P=0.005) and neurodegeneration (HCV atrophy) (R-squared= 0.13; P=0.003) only in females. No association was found between GFAP and AD biomarkers in females or males without cognitive impairment (Fig 2).
Conclusions
Our results suggest astrocyte reactivity is highly associated with AD pathophysiology in females than males. This may have important implications for elucidating the basis of the higher prevalence of AD in females.Yet, these results were generated with a limited number of subjects and using a cross-sectional design. Therefore, replication in larger, independent longitudinal datasets is needed to better understand the association of GFAP levels, sex, and AD.