Evaluation of preanalytical factors on quantification of amyloid-β (1-42), phosphorylated tau 181, and total tau in cerebrospinal fluid

Introduction Cerebrospinal fluid (CSF) biomarkers for Alzheimer disease are US Food and Drug Administration approved and implemented on automated platforms, allowing for widespread use and higher throughput. Although low-bind polypropylene tubes for accurate quantification of amyloid-β (Aβ) have been well studied, less is known about the impact of other common preanalytical variables on quantification of biomarkers for Alzheimer disease. This study evaluated the effects of refrigerated transportation and hemolysis on the concentrations of Aβ42, phosphorylated tau 181, and total tau. Methods The Roche Diagnostics Elecsys β-Amyloid (1-42) CSF II, Elecsys Phospho-Tau (181P) CSF, and Elecsys Total-Tau CSF assays were used on the Roche cobas pro e 801 platform to measure protein concentrations in residual CSF samples. Paired-difference testing was performed to determine the effects of simulated transportation and hemolysis on each analyte. Results For all 3 analytes, less than 10% difference was observed between the concentrations measured on day 0 and after 14 days of transportation and refrigeration. In contrast, 2.26 g/L free hemoglobin resulted in more than 10% negative bias in Aβ42 measurement compared with the 0 g/L control but did not affect phosphorylated tau 181 or total tau concentrations. Discussion Refrigerated transportation did not affect the analysis of Aβ42, phosphorylated tau 181, or total tau, whereas hemolysis can negatively affect results of Aβ42.