Astrogliosis and episodic memory in late life: higher GFAP is related to worse memory and white matter microstructure in healthy aging and Alzheimer's disease

Abstract

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e., Aβ42) and neurodegeneration (i.e., total tau; neurofilament light chain) in 114 older adults (asymptomatic, n = 69; MCI/AD dementia, n = 45). Higher levels of GFAP were associated with lower memory scores (p < 0.0001), such that for 1 SD increase in mean GFAP values, the memory composite score decreased on average by 0.49 (Standard error = 0.071). These results remained significant after controlling for diagnostic status and AD-related blood biomarkers. Higher GFAP was also related to lower WM integrity in regions vulnerable to AD pathology; however, WM integrity did not account for the association between GFAP and memory. Study findings suggest that higher blood levels of a marker of astrogliosis may reflect impoverished memory functions and white matter health, independent of markers of amyloid or neurodegeneration.

Keywords: Aging; Alzheimer's disease; Astrocytes; Astrogliosis; Memory.