Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease

Authors

Pratishtha Chatterjee, Edith Cowan UniversityFollow
Steve Pedrini, Edith Cowan UniversityFollow
Nicholas J. Ashton
Michelle Tegg, Edith Cowan UniversityFollow
Kathryn Goozee
Abhay K. Singh
Thomas K. Karikari
Joel Simrén
Eugeen Vanmechelen
Nicola J. Armstrong
Eugene Hone, Edith Cowan UniversityFollow
Prita R. Asih
Kevin Taddei, Edith Cowan UniversityFollow
Vincent Doré
Victor L. Villemagne
Hamid R. Sohrabi, Edith Cowan UniversityFollow
Henrik Zetterberg
Colin L. Masters
Kaj Blennow
Ralph N. Martins, Edith Cowan UniversityFollow

Document Type

Journal Article

Publication Title

Alzheimer's and Dementia

Volume

18

Issue

6

First Page

1141

Last Page

1154

PubMed ID

34494715

Publisher

Wiley

School

School of Medical and Health Sciences

RAS ID

38867

Funders

Australian Alzheimer’s Research Foundation / Swedish Research Council,Grant / Award Number: #2018-02532 / European Research Council,Grant / Award Number: #681712 / Swedish State Support for Clinical Research, Grant / Award Number: #ALFGBG-720931 / Alzheimer Drug Discovery Foundation (ADDF), USA, Grant / Award Number: #201809-2016862, #RDAPB-201809-2016615 / UK Dementia Research Institute at UCL / Swedish Alzheimer Foundation, Grant / Award Number: #AF-742881 / Hjärnfonden, Sweden, Grant / Award Number: #FO2017-0243

Comments

Chatterjee, P., Pedrini, S., Ashton, N. J., Tegg, M., Goozee, K., Singh, A. K., ... & Martins, R. N. (2022). Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease. Alzheimer's & Dementia, 18(6), 1141-1154. https://doi.org/10.1002/alz.12447

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.

DOI

10.1002/alz.12447

Related Publications

Pedrini, S. (2023). An overview of blood-based biomarkers in AD. https://ro.ecu.edu.au/theses/2623

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