Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias. (1st December 2020)

• Record Type: Journal Article
• Authors: Hanes, Jozef; Kovac, Andrej; Kvartsberg, Hlin; Kontsekova, Eva; Fialova, Lubica; Katina, Stanislav; Kovacech, Branislav; Stevens, Eva; Hort, Jakub; Vyhnalek, Martin; Boonkamp, Lynn; Novak, Michal; Zetterberg, Henrik; Hansson, Oskar; Scheltens, Philip; Blennow, Kaj; Teunissen, Charlotte E.; Zilka, Norbert
• Is Part Of: Neurology. Volume 95:Number 22(2020)
• Publication Date: 2020-12-01
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000010814
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To investigate whether tau phosphorylated at Thr217 (p-tau T217) assay in CSF can distinguish patients with Alzheimer disease (AD) from patients with other dementias and healthy controls. Methods: We developed and validated a novel Simoa immunoassay to detect p-tau T217 in CSF. There was a total of 190 participants from 3 cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy participants (n = 44). Results: The p-tau T217 assay (cutoff 242 pg/mL) identified patients with AD with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, and 88% specificity, compared favorably with p-tau T181 ELISA (52 pg/mL), showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity, and 97% sensitivity. The assay distinguished patients with AD from age-matched healthy controls (cutoff 163 pg/mL, 98% sensitivity, 93% specificity), similarly to p-tau T181 ELISA (cutoff 60 pg/mL, 96% sensitivity, 86% specificity). In patients with AD, we found a strong correlation between p-tau T217 and p-tau T181, total tau and β-amyloid 40, but not β-amyloid 42. Conclusions: This study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggest that the new p-tau T217 assay has potential as an AD diagnostic test in clinical evaluation. Classification of evidence: This study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes patients with AD from patients with other dementias and healthy controls.