In Alzheimer's disease (AD) research, cerebrospinal fluid (CSF) Amyloid beta (Aβ), Tau and pTau are the most accepted and well validated biomarkers. Several methods and platforms exist to measure those biomarkers, leading to challenges in combining data across studies. Thus, there is a need to identify methods that harmonize and standardize these values. We used a Z-score based approach to harmonize CSF and amyloid imaging data from multiple cohorts and compared GWAS results using this approach with currently accepted methods. We also used a generalized mixture model to calculate the threshold for biomarker-positivity. Based on our findings, our normalization approach performed as well as meta-analysis and did not lead to any spurious results. In terms of dichotomization, cutoffs calculated with this approach were very similar to those reported previously. These findings show that the Z-score based harmonization approach can be applied to heterogeneous platforms and provides biomarker cut-offs consistent with the classical approaches without requiring any additional data.

Original languageEnglish
Article number106373
JournalNeurobiology of Disease
StatePublished - Jan 2024


  • Alzheimer's
  • Biomarkers
  • Dichotomization
  • Harmonization
  • Imaging
  • Meta-analysis
  • Mixture modelling
  • Z-scores


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