P1–250: Development and Characterization of a Validated Multiplex Panel for Detection of Beta‐amyloid Peptides in Human CSF

Considered along with neuropsychological and/or neuroimaging data, baseline AD biomarker profiles may be used to stratify and enrich particular patient populations, which may enhance the success of clinical trials and natural history studies. However, challenges with existing AD biomarker assays, including issues with repeatability and reproducibility within and across centers and across manufactured lots, limit their clinical utility. Herein, we report development and analytical validation of a human A b peptide multiplex panel for measurement of A b 38, A b 40, and A b 42 in human CSF using fit-for-purpose and Clinical and Laboratory Standards Institute principles. The panel was developed using MSD's MULTI-ARRAY® technology and was optimized to minimize CSF matrix effects and interferences. Analytical validation was performed across multiple panel lots to verify consistency in sensitivity, accuracy, and precision. The human A b peptide panel demonstrated excellent sensitivity, performance, and inter-lot reproducibility. Measured levels of the three A b peptides in human CSF fell within the quantitative ranges of the assays and were consistent with literature reports. Assay precision, accuracy, and total error were determined from human CSF control samples. Dilution linearity and spike recovery testing demonstrated minimal matrix effects and accurate quantitation of A b peptide over the range of the assays. The assays showed no significant cross-reactivity or interference from closely related A b peptides. The human A b peptide panel was developed and analytically validated to measure A b 38, A b 40, and A b 42 in human CSF. The panel had good analytical performance characteristics, inter-lot consistency, and the ability to measure A b peptide levels in human CSF samples. This panel will support ongoing efforts to standardize AD biomarker testing and opens the door to multiplexing with other key biomarker assays such as phosphorylated and total tau.