Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer’s disease continuum

Congratulations to Drs. David Vaillancourt, Melissa Armstrong and Steven DeKosky on the publication of “Moderating effects of plasma glial fibrillary acidic protein along the Alzheimer’s disease continuum,” which appears in the September issue of Alzheimer’s and Dementia.

Abstract

INTRODUCTION

Glial fibrillary acidic protein (GFAP) may contribute to Alzheimer’s pathology at early disease stages. GFAP moderation of Alzheimer’s disease (AD)‐related neurodegeneration and cognition is unclear.

METHODS

We examined plasma GFAP moderation of AD biomarkers (amyloid beta [Aβ]‐positron emission tomography [PET][A]; plasma phosphorylated tau‐181 [p‐tau181][T1]), neurodegeneration (plasma NfL[Nplasma]; structural magnetic resonance imaging [MRI][NMRI]), and cognition (Cogmemory; Cogexecutive) in two cohorts: University of California San Francisco (UCSF) (N = 212, 91.0% non‐Hispanic/Latino White [NHLW], age = 74.7 [7.6] years, 75.9% cognitively unimpaired [CU]) and 1Florida Alzheimer’s Disease Research Centers (1FLADRC; N = 582, 32.8% NHLW, age = 70.7 [8.5] years, 28.9% CU).

RESULTS

Plasma GFAP consistently moderated A–T1 (UCSF: β = 0.46, p = 0.012; 1FLADRC: β = 0.12, = 0.029). The association between elevated Aβ‐PET and increased (p‐tau) was strengthened at higher GFAP concentrations. In 1FLADRC, GFAP moderated T1–Nplasma/MRI. In UCSF, GFAP moderated T1–Cogmemory/executive and NMRI–Cogmemory/executive. Higher GFAP consistently related to worse neurodegeneration and cognition (main effects).

DISCUSSION

Across demographically and clinically heterogeneous cohorts, plasma GFAP is a key moderator of AD and may help identify individuals at greatest risk of AD‐related neurodegeneration and cognitive decline.