Harmonization and standardization of biofluid‐based biomarker measurements for AT(N) classification in Alzheimer's disease

Abstract Fluid biomarkers are currently measured in cerebrospinal fluid and blood for Alzheimer's disease diagnosis and are promising targets for drug development and for patients’ follow‐up in clinical trials. These biomarkers have been grouped in an unbiased research framework, the amyloid (Aβ), tau, and neurodegeneration (AT[N]) biomarker system to aid patients’ early diagnosis and stratification. Metrological approaches relying on mass spectrometry have been used for the development of reference materials and reference measurement procedures. Despite their excellent performances as clinical tools, fluid biomarkers often present an important between‐laboratory variation. Standardization efforts were carried out on the biomarkers currently included in the AT(N) classification system, involving the collaboration of national metrology institutes, clinicians, researchers, and in vitro diagnostic providers. This article provides an overview of current activities towards standardization. These reference methods and reference materials may be used for recalibration of immunoassays and the establishment of standardized cutoff values allowing a better stratification of Alzheimer's disease patients. Highlights The AT(N) biomarker system allows stratifying AD patients on the basis of biomarker profiles. Fluid biomarker measurements often present an important between‐laboratory variation preventing the establishment of standardized cutoff values. Overview on the standardization initiatives involving the fluid biomarkers currently included in the AT(N) framework.