Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias
Language English Country United States Media print-electronic
Document type Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
32973122
PubMed Central
PMC7734919
DOI
10.1212/wnl.0000000000010814
PII: WNL.0000000000010814
Knihovny.cz E-resources
- MeSH
- Alzheimer Disease cerebrospinal fluid diagnosis MeSH
- Amyloid beta-Peptides cerebrospinal fluid MeSH
- Diagnosis, Differential MeSH
- Frontotemporal Dementia cerebrospinal fluid diagnosis MeSH
- Immunoassay methods standards MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Neurodegenerative Diseases cerebrospinal fluid diagnosis MeSH
- Peptide Fragments cerebrospinal fluid MeSH
- Predictive Value of Tests MeSH
- Aphasia, Primary Progressive cerebrospinal fluid diagnosis MeSH
- Supranuclear Palsy, Progressive cerebrospinal fluid diagnosis MeSH
- tau Proteins cerebrospinal fluid MeSH
- Reproducibility of Results MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Tauopathies cerebrospinal fluid diagnosis MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- amyloid beta-protein (1-40) MeSH Browser
- amyloid beta-protein (1-42) MeSH Browser
- Amyloid beta-Peptides MeSH
- MAPT protein, human MeSH Browser
- Peptide Fragments MeSH
- tau Proteins MeSH
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.
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