Cullen, NC;
Janelidze, S;
Mattsson-Carlgren, N;
Palmqvist, S;
Bittner, T;
Suridjan, I;
Jethwa, A;
... Hansson, O; + view all
(2022)
Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models.
Alzheimer's & Dementia
10.1002/alz.12706.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12706 |
| Publisher version: | https://doi.org/10.1002/alz.12706 |
| Language: | English |
| Additional information: | © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | Diagnosis, gray zones, plasma biomarkers, random error, test-retest variability |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10150622 |
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