UC San Diego

BACKGROUND: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-β 1-42 peptide (Aβ42) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis. OBJECTIVE: To validate the analytical and clinical performance of the MSD t-tau and Aβ42 kits and propose diagnostic cut-off values for the field. METHODS: The analytical performance of the CSF t-tau and Aβ42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, Aβ42, and t-tau/Aβ42 in three clinically characterized cohorts. RESULTS: Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/Aβ42 performed the best. CONCLUSIONS: Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and Aβ42 assays. Based on a large, multi-center, clinically-diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, Aβ42, and t-tau/Aβ42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories.