Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias
Open Access
- 1 December 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 95 (22), e3026-e3035
- https://doi.org/10.1212/wnl.0000000000010814
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.This publication has 26 references indexed in Scilit:
- A Practical Guide to Immunoassay Method ValidationFrontiers in Neurology, 2015
- Neuronal activity regulates extracellular tau in vivoThe Journal of Experimental Medicine, 2014
- Criteria for the diagnosis of corticobasal degenerationNeurology, 2013
- Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: A consensus paper from the Alzheimer's Biomarkers Standardization InitiativeAlzheimer's & Dementia, 2011
- Classification of primary progressive aphasia and its variantsNeurology, 2011
- Staging of Neurofibrillary Pathology in Alzheimer's Disease: A Study of the BrainNet Europe ConsortiumBrain Pathology, 2008
- Endocytosis Is Required for Synaptic Activity-Dependent Release of Amyloid-β In VivoNeuron, 2008
- CSF biomarkers for Alzheimer’s disease: use in early diagnosis and evaluation of drug treatmentExpert Review of Molecular Diagnostics, 2005
- Deposition of β-Amyloid Subtypes 40 and 42 Differentiates Dementia With Lewy Bodies From Alzheimer DiseaseArchives of Neurology, 1999
- THE FREQUENCY DISTRIBUTION OF THE PRODUCT-MOMENT CORRELATION COEFFICIENT IN RANDOM SAMPLES OF ANY SIZE DRAWN FROM NON-NORMAL UNIVERSESBiometrika, 1951