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.