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

Details

Serval ID
serval:BIB_17AF548CA0F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization.
Journal
Journal of Alzheimer's disease
Author(s)
Lewczuk P., Lelental N., Lachmann I., Holzer M., Flach K., Brandner S., Engelborghs S., Teunissen C.E., Zetterberg H., Molinuevo J.L., Mroczko B., Blennow K., Popp J., Parnetti L., Chiasserini D., Perret-Liaudet A., Spitzer P., Maler J.M., Kornhuber J.
ISSN
1875-8908 (Electronic)
ISSN-L
1387-2877
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
55
Number
1
Pages
159-170
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Virtually nothing is known about a potential diagnostic role of non-phospho-epitopes of Tau (Non-P-Tau) in cerebrospinal fluid (CSF).
To establish and analytically and clinically characterize the first assay capable to measure concentrations of Non-P-Tau in human CSF.
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.
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.
For the first time, an assay is reported to reliably measure concentrations of non-phosphorylated Tau in human CSF.

Keywords
Aged, Alzheimer Disease/cerebrospinal fluid, Animals, Biomarkers/cerebrospinal fluid, Cells, Cultured, Cognitive Dysfunction/cerebrospinal fluid, Enzyme-Linked Immunosorbent Assay/methods, Epitope Mapping, Female, Humans, Immunoglobulin G, Male, Mice, Inbred BALB C, Phosphorylation, Protein Stability, Reproducibility of Results, Sensitivity and Specificity, Specimen Handling/methods, Temperature, tau Proteins/cerebrospinal fluid, tau Proteins/genetics, Biomarkers, cerebrospinal fluid, phosphorylation, tau
Pubmed
Web of science
Create date
08/12/2016 16:53
Last modification date
20/08/2019 12:47
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