Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models.

Abstract

INTRODUCTION:

The effect of random error on the performance of blood-based biomarkers for Alzheimer's disease (AD) must be determined before clinical implementation.

METHODS:

We measured test-retest variability of plasma amyloid beta (Aβ)42/Aβ40, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p-tau)217 and simulated effects of this variability on biomarker performance when predicting either cerebrospinal fluid (CSF) Aβ status or conversion to AD dementia in 399 non-demented participants with cognitive symptoms.

RESULTS:

Clinical performance was highest when combining all biomarkers. Among single-biomarkers, p-tau217 performed best. Test-retest variability ranged from 4.1% (Aβ42/Aβ40) to 25% (GFAP). This variability reduced the performance of the biomarkers (≈ΔAUC [area under the curve] -1% to -4%) with the least effects on models with p-tau217. The percent of individuals with unstable predicted outcomes was lowest for the multi-biomarker combination (14%).

DISCUSSION:

Clinical prediction models combining plasma biomarkers-particularly p-tau217-exhibit high performance and are less effected by random error. Individuals with unstable predicted outcomes ("gray zone") should be recommended for further tests.

• Authors: Nicholas C Cullen, Shorena Janelidze, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Tobias Bittner, Ivonne Suridjan, Alexander Jethwa, Gwendlyn Kollmorgen, Wagner S Brum, Henrik Zetterberg, Kaj Blennow, Erik Stomrud, Oskar Hansson
• Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) (Jun 14 2022) ISSN: 1552-5279 [Electronic] United States
• PMID: 35699240 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.