CSF TAU proteins in differential diagnosis of dementia

Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) represent an important differential diagnostic problem in clinical practice. The identification for new biomarkers that would help establishing the diagnosis and primary cause of the dementia is therefore highly relevant. The aim of this study was to investigate the diagnostic accuracy of three potential CSF biomarkers, total tau protein (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), and tau protein phosphorylated at serine 199 (p-tau199) in the differential diagnosis of AD and FTLD patients in relatively young age groups. The concentrations of the three CSF biomarkers were measured in 25 FTLD patients, 27 AD patients, and 25 non-demented (ND) subjects. The CSF concentrations of all three markers were significantly higher in AD than in FTLD cases (p < 0.001) or ND controls (p < 0.001). No difference was observed in FTLD compared to the ND group, except for p-tau181 (p = 0.028). When sensitivity was set at 85% or higher, specificity in differentiation between FTLD and AD patients reached 40% for t-tau, 37.5% for p-tau181 and 56% for p-tau199. Improvement of the diagnostic accuracy upon logistic regression analysis with t-tau and p-tau199 as independent variables showed that 22 out of 25 FTLD patients could be correctly classified. In conclusion, none of the markers per se fulfilled the criteria for the "ideal" marker (sensitivity and specificity higher than 85%). However, combination of t-tau and p-tau199 classified correctly 88% of FTLD patients, thus largely satisfying practical requirements.