The CentiMarker project: Standardizing quantitative Alzheimer's disease fluid biomarkers for biologic interpretation

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Abstract
INTRODUCTION: Biomarkers play a crucial role in understanding Alzheimer's disease (AD) pathogenesis and treatment effects. However, comparing biomarker measures without standardization and appreciating their magnitude relative to the disease can be challenging.METHODS: To address this issue, we propose the CentiMarker approach, similar to Centiloid, which provides a standardized scale between normal (0) and nearly maximum abnormal AD (100) ranges. We applied this scale to cerebrospinal fluid (CSF) biomarkers in dominantly inherited AD and sporadic AD cohorts.RESULTS: CentiMarkers facilitated the interpretation of disease abnormality, demonstrating comparable changes and distributions of AD biomarkers across disease stages. CentiMarkers make the treatment effect more comparable than their original scales across various biomarkers.DISCUSSION: The versatility of CentiMarkers makes it a valuable tool for standardized biomarker comparison in AD research, enabling informed cross‐study comparisons and contributing to accelerated therapeutic development. Adoption of the CentiMarker scale could enhance biomarker reporting and advance our understanding of AD.Highlights: Comparing fluid biomarkers without appreciating their magnitude relative to the disease can be challenging. We propose a CentiMarker metric to standardize biomarker measures from normal (0) and nearly maximum abnormal AD (100) ranges. CentiMarkers make the treatment effect more comparable across various biomarkers than when using the original scales.
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Funding Information
  • National Institute on Aging
  • National Institutes of Health (U01 AG024904, U01AG042791‐S1)
  • Alzheimer's Association
  • Eli Lilly and Company
  • Avid Radiopharmaceuticals
  • GHR Foundation
  • Alzheimer's Disease Neuroimaging Initiative
  • U.S. Department of War (W81XWH‐12‐2‐0012)
  • National Institute of Biomedical Imaging and Bioengineering
  • Foundation for the National Institutes of Health (U01AG052564)

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