Validation of a Commercial Chemiluminescence Immunoassay for the Simultaneous Measurement of Three Different Amyloid-ß Peptides in Human Cerebrospinal Fluid and Application to a Clinical Cohort.

A comprehensive assay validation campaign of a commercially available chemiluminescence multiplex immunoassay for the simultaneous measurement of the amyloid-ß peptides Aß38, Aß40, and Aß42 in human cerebrospinal fluid (CSF) is presented. The assay quality parameters we addressed included impact of sample dilution, parallelism, lower limits of detection, lower limits of quantification, intra- and inter-assay repeatability, analytical spike recoveries, and between laboratory reproducibility of the measurements. The assay performed well in our hands and fulfilled a number of predefined acceptance criteria. The CSF levels of Aß40 and Aß42 determined in a clinical cohort (n = 203) were statistically significantly correlated with available ELISA data of Aß1-40 (n = 158) and Aß1-42 (n = 179) from a different laboratory. However, Bland-Altman method comparison indicated systematic differences between the assays. The data presented here furthermore indicate that the CSF concentration of Aß40 can surrogate total CSF Aß and support the hypothesis that the Aß42/Aß40 ratio outperforms CSF Aß42 alone as a biomarker for Alzheimer's disease due to a normalization to total Aß levels.