Diagnostic Values of Cerebrospinal Fluid T-Tau and Aß42 using Meso Scale Discovery Assays for Alzheimer's Disease.

ABSTRACT

BACKGROUND: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-ß 1-42 peptide (Aß42) 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 Aß42 kits and propose diagnostic cut-off values for the field. METHODS: The analytical performance of the CSF t-tau and Aß42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, Aß42, and t-tau/Aß42 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/Aß42 performed the best. CONCLUSIONS: Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and Aß42 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, Aß42, and t-tau/Aß42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories.