title: 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-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.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Ané
authors.initials: A
authors.lastname: Korff
authors.affiliation: Department of Neurosciences, University of California at San Diego, San Diego, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ginghina
authors.affiliation: Northwest Network VISN-20 Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Peskind
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR, USA Portland VA Medical Center, Portland, OR, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Quinn
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.affiliation: Department of Biostatistics, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cain
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001057:Apolipoproteins E / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Aβ$^{42}$; Meso Scale Discovery; cerebrospinal fluid; tau