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A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Dumurgier, Julien; Sabia, Séverine; Zetterberg, Henrik; Teunissen, Charlotte; Hanseeuw, Bernard; Orellana, Adelina; Schraen, Susanna; ... for the Alzheimer’s Disease Neuroimaging Initiative, .; + view all (2022) A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging. Neurology , 99 (7) e669-e678. 10.1212/WNL.0000000000200735. Green open access

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Abstract

OBJECTIVE: To elaborate a new algorithm to establish a standardized method to define cuff-offs for CSF biomarkers of Alzheimer's disease (AD) by validating the algorithm against CSF classification derived from PET imaging. METHODS: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cut-offs for CSF amyloid-β peptide (Aβ) biomarkers. These Aβ cut-offs were then used to determine cut-offs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. RESULTS: A total of 6,922 subjects with CSF biomarkers data were included (mean (SD) age: 70.6 (8.5) years, 51.0% women). In the ADNI study population (n=497), the agreement between classification based on our algorithm and one based on amyloid/tau PET imaging was high with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n=6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. DISCUSSION: The proposed novel, pragmatic method to determine CSF biomarkers cut-offs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.

Type: Article
Title: A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000200735
Publisher version: https://doi.org/10.1212/WNL.0000000000200735
Language: English
Additional information: © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: CSF biomarkers, Alzheimer's disease, All epidemiology, cut-offs
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
URI: https://discovery.ucl.ac.uk/id/eprint/10150373
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