Johnson, Sterling C.Suárez-Calvet, MarcSuridjan, IvonneMinguillón, CarolinaGispert López, Juan DomingoJonaitis, ErinMichna, AgathaCarboni, MargheritaBittner, TobiasRabe, ChristinaKollmorgen, GwendlynZetterberg, HenrikBlennow, Kaj2023-12-182023-12-182023Johnson SC, Suárez-Calvet M, Suridjan I, Minguillón C, Gispert JD, Jonaitis E, Michna A, Carboni M, Bittner T, Rabe C, Kollmorgen G, Zetterberg H, Blennow K. Identifying clinically useful biomarkers in neurodegenerative disease through a collaborative approach: the NeuroToolKit. Alzheimers Res Ther. 2023 Jan 28;15(1):25. DOI: 10.1186/s13195-023-01168-y1758-9193http://hdl.handle.net/10230/58552Background: 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.application/pdfeng© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made availableinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1186/s13195-023-01168-yAlzheimer’s diseaseAmyloid-βCerebrospinal fluid biomarkersGlial activationInflammationNeurodegenerationinfo:eu-repo/semantics/openAccess