Novel immunoassay detecting p-Tau Thr217 distinguishes Alzheimer’s Disease from other dementias

Objective To investigate whether p-tau T217 assay in cerebrospinal fluid (CSF) can distinguishes Alzheimer’s disease from 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 three cohorts with AD (n = 77) and other neurodegenerative diseases (n = 69) as well as healthy subjects (n = 44). Results The p-tau T217 assay (cut-off 242 pg/ml) identified AD subjects with accuracy of 90%, with 78% positive predictive value (PPV), 97% negative predictive value (NPV), 93% sensitivity, 88% specificity compared favorably with p-tau T181 ELISA (52 pg/ml) showing 78% accuracy, 58% PPV, 98% NPV, 71% specificity; 97% sensitivity. The assay distinguished AD patients from age-matched healthy subjects (cut-off 163 pg/ml, sensitivity 98%, specificity 93%) similarly to p-tau T181 ELISA (cut-off 60 pg/ml, 96% sensitivity and 86% specificity). In AD patients, we found a strong correlation between p-tau T217-tau and p-tau T181, t-tau and Aβ40 but not with Aβ42. Conclusions This study demonstrates that p-tau T217 displayed better diagnostic accuracy than p-tau T181. The data suggests that new p-tau T217 assay has a potential as an AD diagnostic test in the clinical evaluation. Classification of Evidence: This study provides Class III evidence that a CSF immunoassay for p-tau T217 distinguishes AD from other dementias and healthy controls.