Title | Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Lewczuk, P, Lelental, N, Lachmann, I, Holzer, M, Flach, K, Brandner, S, Engelborghs, S, Teunissen, CE, Zetterberg, H, Molinuevo, JLuis, Mroczko, B, Blennow, K, Popp, J, Parnetti, L, Chiasserini, D, Perret-Liaudet, A, Spitzer, P, Maler, JManuel, Kornhuber, J |
Journal | J Alzheimers Dis |
Volume | 55 |
Issue | 1 |
Pagination | 159-170 |
Date Published | 2017 |
ISSN | 1875-8908 |
Abstract | 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 CONCLUSION: For the first time, an assay is reported to reliably measure concentrations of non-phosphorylated Tau in human CSF. |
DOI | 10.3233/JAD-160448 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 27662295 |