Harmonization of CSF and imaging biomarkers for Alzheimer's disease biomarkers: need and practical applications for genetics studies and preclinicalclassification

Abstract

INTRODUCTIONIn Alzheimers disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (A{beta}), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers which leads to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. METHODSWe used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS result using this method with currently accepted methods. We also used a generalized mixture modelling to calculate the threshold for biomarker-positivity. RESULTSZ-scores method performed as well as meta-analysis and did not lead to any spurious results. Cutoffs calculated with this approach were found to be very similar to those reported previously. DISCUSSIONThis approach can be applied to heterogeneous platforms and provides biomarker cut-offs consistent with the classical approaches without requiring any additional data.