Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization

Lewczuk P, Lelental N, Lachmann I, Holzer M, Flach K, Brandner S, Engelborghs S, Teunissen CE, Zetterberg H, Luis Molinuevo J, Mroczko B, Blennow K, Popp J, Parnetti L, Chiasserini D, Perret-Liaudet A, Spitzer P, Maler JM, Kornhuber J (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 55

Pages Range: 159-170

Journal Issue: 1

DOI: 10.3233/JAD-160448

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 < 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.

Authors with CRIS profile

Involved external institutions

Università degli Studi di Perugia Italy (IT) University of Antwerp / Universiteit Antwerpen Belgium (BE) AJ Roboscreen GmbH Germany (DE) University of Białystok Poland (PL) Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Spain (ES) University of Gothenburg / Göteborgs universitet Sweden (SE) Hospices Civils de Lyon (CHU) France (FR) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Universität Leipzig Germany (DE) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) Switzerland (CH)

How to cite

APA:

Lewczuk, P., Lelental, N., Lachmann, I., Holzer, M., Flach, K., Brandner, S.,... Kornhuber, J. (2017). Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization. Journal of Alzheimer's Disease, 55(1), 159-170. https://doi.org/10.3233/JAD-160448

MLA:

Lewczuk, Piotr, et al. "Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization." Journal of Alzheimer's Disease 55.1 (2017): 159-170.

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