Diagnostic Values of Cerebrospinal Fluid T-Tau and Aβ₄₂ using Meso Scale Discovery Assays for Alzheimer's Disease

Article type: Research Article

Authors: Pan, Catherine^{a; 1} | Korff, Ané^{a; 1} | Galasko, Douglas^b | Ginghina, Carmen^a | Peskind, Elaine^{c; d} | Li, Ge^{d; e} | Quinn, Joseph^{f; g} | Montine, Thomas J.^a | Cain, Kevin^h | Shi, Min^a | Zhang, Jing^{a; *}

Affiliations: [a] Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA | [b] Department of Neurosciences, University of California at San Diego, San Diego, CA, USA | [c] Northwest Network VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA | [d] Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA | [e] Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA | [f] Department of Neurology, Oregon Health and Science University, Portland, OR, USA | [g] Portland VA Medical Center, Portland, OR, USA | [h] Department of Biostatistics, University of Washington School of Medicine, Seattle, WA, USA

Correspondence: [*] Correspondence to: Jing Zhang, Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Avenue, Seattle, WA 98104, USA. Tel.: +1 206 897 5245; Fax: +1 206 897 5249; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Aβ₄₂, Alzheimer's disease, cerebrospinal fluid, Meso Scale Discovery, tau

DOI: 10.3233/JAD-143099

Journal: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 709-719, 2015