Improved Performance of CSF Dementia Biomarker Measurements Over Time: The Effect of Quality Control and Harmonization Programs

Abstract

Introduction: Cerebrospinal Fluid (CSF) biomarkers Total Tau Protein (τT), Amyloid Beta Peptide (Aβ42) and tau protein hyper phosphorylated at threonine 181 (τP-181) are important in the (differential) diagnosis of dementia and analysis of these biomarkers is now incorporated in the diagnostic criteria of Alzheimer’s disease. However, lack of standardization has led to considerable interand intra-laboratory variation. Various international programs have been launched aiming in the reduction of variability and harmonization of biomarker measurements. Objectives: To explore whether experience gained from international quality control and harmonization programs had any effect on the analytical performance of our laboratory for CSF dementia biomarkers [Total Tau (τT), Amyloid Beta (Aβ42) and PhosphoTau (τP-181)]. Methods: We retrospectively analyzed internal standard measurements during ELISA runs in 3 time periods: before 2010, 2010-2012 (experience from workshops and quality control programs) and after 2012 (JPND-BIOMARKAPD harmonization program). Results: During the 1st period, coefficients of variation were 8.6%-17.1%. Subsequently, they were reduced, reaching 4.5%6.6% at the 3rd period. Measurement error was reduced for τT and Aβ42 from 9.2% and 22.1% to 1% and 3.3% respectively. Median values for Aβ42 were significantly lower compared to the expected values during the 1st period but, came closer to (at the 2nd period) and finally reached the expected value at the 3rd period. Conclusion: The improvement noted, indicates a beneficial effect of quality control and harmonization programs on analytical performance, by lowering measurement errors to levels which are not expected to adversely affect diagnostic performance in every day practice. . DOI: 10.29011/BMAP-126. 100026