Current practices and harmonization challenges in Alzheimer's disease biomarkers: an EFLM Committee: Harmonization...

Fluid biomarkers are central to the biological definition and diagnosis of Alzheimer's disease (AD). Despite international recommendations, substantial variability persists in laboratory practices. This survey, promoted by the Committee: Harmonisation (C:H) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), aimed to assess real-world laboratory practices for AD biomarker testing.

An online survey was distributed to EFLM members. The questionnaire addressed pre-analytical, analytical, and post-analytical practices for cerebrospinal fluid (CSF) and blood-based AD biomarkers. Descriptive statistics were applied.

A total of 316 responses from more than 35 countries were collected. CSF remained the primary matrix for AD diagnostics, although blood-based biomarkers were increasingly implemented. Marked heterogeneity was observed across all phases of testing, including sample handling, assay platforms, biomarker panels, and decisional cut-offs. Cut-off values for core biomarkers varied widely, as well as harmonization of reporting unit and the adoption of SI units preventing a shared approach to interpreting the results.

Despite growing clinical adoption, AD biomarker testing remains highly heterogeneous. Coordinated international harmonization of pre-analytical procedures, analytical methods, and post-analytical interpretation, particularly for blood-based biomarkers, is urgently required to ensure reliable and comparable results.