Tau and p-tau as CSF biomarkers in dementia: a meta-analysis

Background: To evaluate the value of total tau (tau) and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) in the differential diagnosis of dementia, more specifically: dementia with Lewy Bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD), and Creutz-feldt-Jacob disease (CJD). Methods: A systematic literature search was performed to identify studies on tau and p-tau in DLB, FTLD, VaD and CJD. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta-analysis. Outcome measures were Cohen's delta, sensitivity and specificity. Results: Compared to controls, tau concentrations are moderately elevated in DLB, FTLD and VaD, while p-tau concentrations are only slightly elevated in DLB and not elevated in FTLD and VaD. Compared to AD, lower tau concentrations differentiated DLB with a sensitivity of 73% and a specificity of 90%, FTLD with sensitivity and specificity of 74%, and VaD with a sensitivity of 73% and a specificity of 86%. Relative to AD, lower p-tau values differentiated FTLD with a sensitivity of 79% and specificity of 83%, and VaD with a sensitivity of 88% and a specificity of 78%. CJD is characterized by extremely elevated tau concentrations with a sensitivity of 91% and a specificity of 98% vs. AD. Conclusions: CSF tau concentrations in DLB, FTLD and VaD are intermediate between controls and AD patients. Overlap with both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed. CJD is characterized by extremely increased tau values, resulting in a sensitivity and specificity that exceeds 90%.