Alzheimer’s & Dementia | September 8, 2021

Chatterjee P, Pedrini S, Ashton NJ, Tegg M, Goozee K, Singh AK, Karikari TK, Simrén J, Vanmechelen E, Armstrong NJ, Hone E, Asih PR, Taddei K, Doré V, Villemagne VL, Sohrabi HR, Zetterberg H, Masters CL, Blennow K and Martins RN

Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2021

https://doi.org/10.1002/alz.12447

This study was performed using Simoa Homebrew assay(s).

Abstract

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.