%0 Journal Article %J J Alzheimers Dis %D 2017 %T Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization. %A Lewczuk, Piotr %A Lelental, Natalia %A Lachmann, Ingolf %A Holzer, Max %A Flach, Katharina %A Brandner, Sebastian %A Engelborghs, Sebastiaan %A Teunissen, Charlotte E %A Zetterberg, Henrik %A Molinuevo, José Luis %A Mroczko, Barbara %A Blennow, Kaj %A Popp, Julius %A Parnetti, Lucilla %A Chiasserini, Davide %A Perret-Liaudet, Armand %A Spitzer, Philipp %A Maler, Juan Manuel %A Kornhuber, Johannes %X

BACKGROUND: Virtually nothing is known about a potential diagnostic role of non-phospho-epitopes of Tau (Non-P-Tau) in cerebrospinal fluid (CSF).

OBJECTIVE: To establish and analytically and clinically characterize the first assay capable to measure concentrations of Non-P-Tau in human CSF.

METHODS: An antibody (1G2) was developed that selectively binds to the Tau molecule non-phosphorylated at the positions T175 and T181, and was used in establishing a sandwich ELISA capable to measure Non-P-Tau in human CSF, following analytical and clinical validation of the method.

RESULTS: The 1G2 antibody shows decreasing reactivity to tau peptides containing phosphorylation mainly at positions T175 and T181. Detection limit of the assay is 25 pg/ml; the coefficients of variation (CVs) of the optical densities of the repeated standard curves were between 3.6-15.9%. Median intra-assay imprecision of double measurements was 4.8%; inter-assay imprecision was in the range of 11.2% - 15.3%. Non-P-Tau concentrations are stable in the CSF samples sent to distinct laboratories under ambient temperature; inter-laboratory variation was approximately 30%. The Non-P-Tau CSF concentrations were highly significantly increased in patients with Alzheimer's disease in stage of mild cognitive impairment or dementia (AD/MCI, n = 58, 109.2±32.0 pg/mL) compared to the non-demented Controls (n = 42, 62.1±9.3 pg/mL, p < 0.001). At the cut-off of 78.3 pg/mL, the sensitivity and the specificity were 94.8% and 97.6%, respectively.

CONCLUSION: For the first time, an assay is reported to reliably measure concentrations of non-phosphorylated Tau in human CSF.

%B J Alzheimers Dis %V 55 %P 159-170 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27662295?dopt=Abstract %R 10.3233/JAD-160448