Johnson, SC;
Suárez-Calvet, M;
Suridjan, I;
Minguillón, C;
Gispert, JD;
Jonaitis, E;
Michna, A;
... Blennow, K; + view all
(2023)
Identifying clinically useful biomarkers in neurodegenerative disease through a collaborative approach: the NeuroToolKit.
Alzheimer's Research and Therapy
, 15
(1)
, Article 25. 10.1186/s13195-023-01168-y.
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Abstract
BACKGROUND: Alzheimer’s disease (AD) is a complex and heterogeneous disease, which requires reliable biomarkers for diagnosis and monitoring disease activity. Preanalytical protocol and technical variability associated with biomarker immunoassays makes comparability of biomarker data across multiple cohorts difficult. This study aimed to compare cerebrospinal fluid (CSF) biomarker results across independent cohorts, including participants spanning the AD continuum. METHODS: Measured on the NeuroToolKit (NTK) prototype panel of immunoassays, 12 CSF biomarkers were evaluated from three cohorts (ALFA+, Wisconsin, and Abby/Blaze). A correction factor was applied to biomarkers found to be affected by preanalytical procedures (amyloid-β1–42, amyloid-β1–40, and alpha-synuclein), and results between cohorts for each disease stage were compared. The relationship between CSF biomarker concentration and cognitive scores was evaluated. RESULTS: Biomarker distributions were comparable across cohorts following correction. Correlations of biomarker values were consistent across cohorts, regardless of disease stage. Disease stage differentiation was highest for neurofilament light (NfL), phosphorylated tau, and total tau, regardless of the cohort. Correlation between biomarker concentration and cognitive scores was comparable across cohorts, and strongest for NfL, chitinase-3-like protein-1 (YKL40), and glial fibrillary acidic protein. DISCUSSION: The precision of the NTK enables merging of biomarker datasets, after correction for preanalytical confounders. Assessment of multiple cohorts is crucial to increase power in future studies into AD pathogenesis.
| Type: | Article |
|---|---|
| Title: | Identifying clinically useful biomarkers in neurodegenerative disease through a collaborative approach: the NeuroToolKit |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13195-023-01168-y |
| Publisher version: | https://doi.org/10.1186/s13195-023-01168-y |
| Language: | English |
| Additional information: | © 2023 BioMed Central Ltd. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Alzheimer’s disease, Amyloid-β, Cerebrospinal fluid biomarkers, Glial activation, Inflammation, Neurodegeneration |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10164656 |
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