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Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Chatterjee, P., Pedrini, S., Ashton, N.J., Tegg, M., Goozee, K., Singh, A.K., Karikari, T.K., Simrén, J., Vanmechelen, E., Armstrong, N.J.ORCID: 0000-0002-4477-293X, Hone, E., Asih, P.R., Taddei, K., Doré, V., Villemagne, V.L., Sohrabi, H.R.ORCID: 0000-0001-8017-8682, Zetterberg, H., Masters, C.L., Blennow, K. and Martins, R.N. (2021) Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease. Alzheimer's & Dementia . Early View.

Link to Published Version: https://doi.org/10.1002/alz.12447
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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.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Healthy Ageing
Health Futures Institute
Publisher: Wiley
Copyright: © 2021 the Alzheimer's Association
URI: http://researchrepository.murdoch.edu.au/id/eprint/62169
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