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

BACKGROUND: The Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ(1–42), t-tau, and p-tau(181) overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau(rel)), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau(rel) can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. METHODS: 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(1–42), t-tau, p-tau(181), and p-tau(rel) 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. RESULTS: 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(rel) to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau(rel) increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau(rel) when differentiating between AD or non-AD dementias and controls. CONCLUSIONS: The addition of p-tau(rel) to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-017-0275-5) contains supplementary material, which is available to authorized users.