Independent associations of plasma GFAP with amyloid‐β and tau in Alzheimer’s disease

Abstract

AbstractBackgroundGlial fibrillary acidic protein (GFAP) is a reactive astrogliosis biomarker, shown to increase in individuals with preclinical Alzheimer’s disease (AD). First thought to be a great marker of amyloid‐β (Aβ) pathology, recent post‐mortem research has linked it to tau accumulation only. Here we investigate the independent associations of plasma GFAP with imaging markers of AD along the disease spectrum.Method126 individuals from TRIAD cohort underwent [18F]MK6240 tau‐PET and [18F]AZD4694 Aβ‐PET and plasma GFAP assessment using an in‐house assay. Voxel and region of interest regression models evaluated the relationship between PET tracers and plasma GFAP. Models with [18F]AZD4694‐PET as the outcome were adjusted for [18F]MK6240‐PET voxel‐wise and vice‐versa. All models were corrected for age and sex, and RFT was used to correct for multiple comparisons.ResultPlasma GFAP was associated with [18F]AZD4694 signal throughout the cortex (Figure1A), independently of [18F]MK6240. Additionally, it was positively correlated with [18F]MK6240 in the medial temporal and occipital lobes and the anterior cingulate cortex, independently of [18F]AZD4694 (Figure1B). Voxel‐wise findings were confirmed by region‐of‐interest‐based analyses.ConclusionOur findings indicate that plasma GFAP is independently associated with both Aβ and tau pathologies in AD. Aβ‐PET showed associations throughout the entire cortex, suggesting its effectiveness as a reliable marker of Aβ pathology across the AD spectrum. On the other hand, tau‐PET correlations were observed in specific regions associated with memory and behavioral impairments that exhibit early deposition of tau. Overall, these results demonstrate that GFAP, an astrogliosis marker, is independently associated with Aβ and tau.