Decoding the relationship of GFAP in serum with Dementia

Background: Astrocytes are an essential glial cell which express GFAP, a marker of astrocytic activation and structural integrity. A recent study by our group links serum GFAP levels to tau pathology in Alzheimer's disease (AD), suggesting its value as a diagnostic biomarker. Our aim is to examine the GFAP levels in serum (GFAPs) in correlation with various neuropathological variables, specifically focusing on the medial temporal lobe (MTL). Method: In 156 brains from the VARS dementia cohort, we analyzed a set of neuropathological variables including macroscopic data and classification and staging criteria for AD, Lewy Body Pathology (LBP), Cerebrovascular Disease (VD), Hippocampal sclerosis (HS), and TDP‐43 pathology (LATE). Result: First, we observed a correlation between GFAPs and tissue GFAP immunostaining in the entorhinal cortex (r=0.211, p <0.05). Then, we found a correlation of GFAPs with brain weight (r=‐0.366, p <0.001), NIA A (r=0.262, p <0.01), NIA B (r=0.416, p <0.001), NIA C (r=0.256, p <0.01), LPC classification (r=0.218; p <0.01), and with the presence of more combined pathologies with high burden (r=0.28, p <0.001). Besides, we observed a trend of increasing GFAPs values with higher stages of MTL atrophy, Braak tau, HS, and LATE. However, no significant correlation was detected between GFAPs and VD. Finally, a lineal regression model showed that NIA B ( p <0.001), HS (head of the hippocampus) ( p <0.05), and Braak α‐syn stages ( p <0.05) were the best predictors for GFAPs. Conclusion: Our study shows that GFAP in serum correlates with neuropathological variables, specially with tissue tau pathology, supporting the potential of GFAP as a diagnostic biomarker for AD and related pathologies, except for cerebrovascular disease.