Decoding the relationship of GFAP in serum with Dementia

TL;DR

This study explores how serum GFAP levels relate to various brain pathologies in dementia, finding that GFAP correlates with tau pathology and other markers of Alzheimer's disease.

Contribution

The study identifies serum GFAP as a potential biomarker for Alzheimer's pathology, excluding cerebrovascular disease.

Findings

Serum GFAP correlates with tissue GFAP immunostaining in the entorhinal cortex.

GFAP levels correlate with brain weight, AD staging criteria, and combined pathology burden.

NIA B, hippocampal sclerosis, and Braak α-syn stages are the best predictors of serum GFAP levels.

Abstract

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).

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).

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.

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.