Diagnostic Values of Cerebrospinal Fluid T-Tau and Aβ42 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 beta 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.

Quantification of CSF biomarkers using an electrochemiluminescence-based detection system in the differential diagnosis of AD and sCJD

“…Development of quantitative assays for CSF biomarkers on the MSD platform has been discussed in several publications [5,24] but detailed descriptions about their clinical performance for the differential diagnosis of neurodegenerative diseases are very limited.…”

“…In this context, the use of an electrochemiluminescence (ECL)-based detection system developed by Meso Scale Discovery (MSD, Gaithersburg, MD, USA) has been shown to present high sensitivity, reproducibility, recovery rates and low background in the detection of several biomarkers in biological fluids [4,5,24]. However, the analytical and clinical performance of ECL technology in CSF samples has not been explored in detail for the differential diagnosis of neurodegenerative dementias.…”

Mass-Spectrometry-Based Method To Quantify in Parallel Tau and Amyloid β 1–42 in CSF for the Diagnosis of Alzheimer’s Disease

“…Levels of tau and Aβ 1–42 were assessed by MSD immunoassays and published previously (14), which generate comparable data to the commonly used AlzBio3 Luminex assay.…”

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

“…1e – h ), i.e. , whether individuals were Aβ+ or Aβ− and pTau+ or pTau− using the accepted cut-off values 7 , 24 , 25 (see Methods ), where Aβ+ and pTau+ status indicates classical AD pathways 23 . In contrast, APOE3 carriers developed less pronounced BBB changes in HC and PHG with cognitive impairment ( Fig.…”