Cerebrospinal fluid P-tau181P: biomarker for improved differential dementia diagnosis

The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau(181p)) in the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-beta peptide of 42 amino acids (A(beta 1-42)), total tau protein (T-tau), and P-tau(181p) were determined with single analyte ELISA-kits (INNOTEST, Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUG) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUG values was performed by means of DeLong tests. The A(beta 1-42)/P-tau(181p) ratio (AUG = 0.770) performed significantly better than A(beta 1-42) (AUG = 0.677, P = 0.004), T-tau (AUG = 0.592, P < 0.001), and A beta(1-42)/T-tau (AUG = 0.678, P = 0.001), while Ptau(181p) (AUG = 0.720) performed significantly better than T-tau (AUG = 0.592, P < 0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, A beta(1-42)/P-tau(181P) (AUG =0.894) discriminated AD from frontotemporal dementia significantly better than A(beta 1-42) (AUG = 0.776, P = 0.020) and T-tau (AUG = 0.746, P = 0.004), while P-tauisip/T-tau (AUG = 0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to A beta(1-42) (AUG = 0.688, P = 0.004), T-tau (AUG = 0.874, P = 0.040), and A beta(1-42)/P-tau(181P) (AUG = 0.760, P = 0.003). In conclusion, this study demonstrates P-tau(181P) P is an essential component of the AD CSF biomarker panel, and combined assessment of A beta(1-42), Ttau, and P-tau(181p) renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias.