Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models
(2023) In Alzheimer's and Dementia 19(3). p.797-806- 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%... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- diagnosis, gray zones, plasma biomarkers, random error, test-retest variability
- in
- Alzheimer's and Dementia
- volume
- 19
- issue
- 3
- pages
- 797 - 806
- publisher
- Wiley
- external identifiers
-
- pmid:35699240
- scopus:85131768281
- ISSN
- 1552-5260
- DOI
- 10.1002/alz.12706
- language
- English
- LU publication?
- yes
- id
- b678693f-b39c-451a-9c29-e3102f6837da
- date added to LUP
- 2022-10-07 11:26:15
- date last changed
- 2024-09-07 03:16:11
@article{b678693f-b39c-451a-9c29-e3102f6837da, abstract = {{<p>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.</p>}}, author = {{Cullen, Nicholas C. and Janelidze, Shorena and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Bittner, Tobias and Suridjan, Ivonne and Jethwa, Alexander and Kollmorgen, Gwendlyn and Brum, Wagner S. and Zetterberg, Henrik and Blennow, Kaj and Stomrud, Erik and Hansson, Oskar}}, issn = {{1552-5260}}, keywords = {{diagnosis; gray zones; plasma biomarkers; random error; test-retest variability}}, language = {{eng}}, number = {{3}}, pages = {{797--806}}, publisher = {{Wiley}}, series = {{Alzheimer's and Dementia}}, title = {{Test-retest variability of plasma biomarkers in Alzheimer's disease and its effects on clinical prediction models}}, url = {{http://dx.doi.org/10.1002/alz.12706}}, doi = {{10.1002/alz.12706}}, volume = {{19}}, year = {{2023}}, }