CSF Total and Phosphorylated Tau Biomarker Findings in a Large Rapidly Progressive Dementia Cohort (P03.077)

OBJECTIVE: Determine the diagnostic utility of CSF total tau (TTau) versus the ratio of total tau and phosphorylated tau (TTau/PTau) in a cohort of sporadic Jakob-Creutzfeldt disease (sCJD) and non-prion rapidly progressive dementia (npRPD) subjects. Assess sensitivity and specificity of TTau using a literature reported cut-off point, and compare this to tiered cut-off points for TTau/PTau to determine if and at what level this ratio provides better diagnostic accuracy than TTau alone. BACKGROUND: TTau has been reported as a reliable diagnostic maker for differentiating CJD from npRPD patients, but its utility is still not clear. We examined CSF levels for TTau alone compared to the ratio of TTau/PTau. DESIGN/METHODS: Data from medical records was stored in a secure database and queried. Most subjects, including npRPD, were referred as suspected CJD. sCJD patients either were pathology-proven or met UCSF or WHO criteria for probable CJD. Non-prion diagnoses were based on published, or accepted, criteria. Only the first LP in which both biomarkers were assessed was used for subjects with multiple lumbar punctures. RESULTS: TTau and TTau/PTau was evaluated in 55 sCJD and 36 npRPD subjects. Using previously published TTau cut-off point (positive at >1200 pg/mL), the sensitivity was 58% and the specificity 92%. The sensitivity and specificity of TTau/PTau cutoffs of 15, 20, and 25 were 87% and 81%, 76% and 89%, and 65% and 92%, respectively. CONCLUSIONS: Our data suggest that a CSF TTau/PTau ratio ≥ 25 might be a better diagnostic marker than TTau alone at >1200 pg/mL. Disclosure: Dr. Forner has nothing to disclose. Dr. Bechtel has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Geschwind has received personal compensation for activities with Gerson Lehrman Group, Clinical Advisors and MedaCorp, and Eisai, Inc.