Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Introduction: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD). Methods: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ−) or presence (Aβ+) of brain amyloidosis. Results: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ− CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ− CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ− CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume. Discussion: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.