No added diagnostic value of non-phosphorylated tau fraction (p-tau rel ) in CSF as a biomarker for differential dementia diagnosis

The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ , t-tau, and p-tau overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ , t-tau, p-tau , and p-tau were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau when differentiating between AD or non-AD dementias and controls. The addition of p-tau to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.