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

Cullen, Nicholas C. LU ; Janelidze, Shorena LU ; Mattsson-Carlgren, Niklas LU orcid ; Palmqvist, Sebastian LU orcid ; Bittner, Tobias ; Suridjan, Ivonne ; Jethwa, Alexander ; Kollmorgen, Gwendlyn ; Brum, Wagner S. and Zetterberg, Henrik , et al. (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.

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organization
publishing date
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
  • scopus:85131768281
  • pmid:35699240
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
2024-04-18 14:47:49
@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}},
}