Cerebrospinal Fluid P-Tau(181P): 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-β peptide of 42 amino acids (Aβ(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 (AUC) 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 AUC values was performed by means of DeLong tests. The Aβ(1–42)/P-tau(181P) ratio (AUC = 0.770) performed significantly better than Aβ(1–42) (AUC = 0.677, P = 0.004), T-tau (AUC = 0.592, P < 0.001), and Aβ(1–42)/T-tau (AUC = 0.678, P = 0.001), while P-tau(181P) (AUC = 0.720) performed significantly better than T-tau (AUC = 0.592, P < 0.001) to discriminate between AD and the pooled non-AD group. When comparing AD and the individual non-AD diagnoses, Aβ(1–42)/P-tau(181P) (AUC = 0.894) discriminated AD from frontotemporal dementia significantly better than Aβ(1–42) (AUC = 0.776, P = 0.020) and T-tau (AUC = 0.746, P = 0.004), while P-tau(181P)/T-tau (AUC = 0.958) significantly improved the differentiation between AD and Creutzfeldt-Jakob disease as compared to Aβ(1–42) (AUC = 0.688, P = 0.004), T-tau (AUC = 0.874, P = 0.040), and Aβ(1–42)/P-tau(181P) (AUC = 0.760, P = 0.003). In conclusion, this study demonstrates P-tau(181P) is an essential component of the AD CSF biomarker panel, and combined assessment of Aβ(1–42), T-tau, and P-tau(181P) renders, to present date, the highest diagnostic power to discriminate between AD and non-AD dementias.