Non-Phosphorylated Tau as a Potential Biomarker of Alzheimer's Disease: Analytical and Diagnostic Characterization
Autor: | Juan Manuel Maler, Johannes Kornhuber, Sebastiaan Engelborghs, Barbara Mroczko, Philipp Spitzer, Lucilla Parnetti, Charlotte E. Teunissen, Sebastian Brandner, Max Holzer, Natalia Lelental, Armand Perret-Liaudet, Davide Chiasserini, Piotr Lewczuk, Henrik Zetterberg, José Luis Molinuevo, Ingolf Lachmann, Julius Popp, Kaj Blennow, Katharina Flach |
---|---|
Přispěvatelé: | Clinical sciences, Neurology |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Pathology Biomarkers cerebrospinal fluid phosphorylation tau Immunoglobulin G Alzheimer Disease/cerebrospinal fluid 0302 clinical medicine Cerebrospinal fluid Medicine Phosphorylation Cells Cultured Medicine(all) Mice Inbred BALB C biology Protein Stability General Neuroscience Temperature General Medicine 3. Good health Standard curve Psychiatry and Mental health Clinical Psychology protein stability Tau phosphorylation Female Alzheimer's disease Antibody medicine.medical_specialty Specimen Handling/methods Enzyme-Linked Immunosorbent Assay tau Proteins Sensitivity and Specificity Specimen Handling 03 medical and health sciences Cognitive Dysfunction/cerebrospinal fluid Alzheimer Disease mental disorders Animals Humans Cognitive Dysfunction Biomarkers/cerebrospinal fluid Aged Detection limit tau Proteins/cerebrospinal fluid/genetics business.industry Enzyme-Linked Immunosorbent Assay/methods tau Proteins/cerebrospinal fluid Reproducibility of Results medicine.disease Molecular biology epitope mapping 030104 developmental biology Potential biomarkers biology.protein Human medicine reproducibility of results Geriatrics and Gerontology business 030217 neurology & neurosurgery Epitope Mapping |
Zdroj: | Journal of Alzheimer's Disease, Vol. 55, No 1 (2017) pp. 159-170 Journal of Alzheimer's Disease Journal of Alzheimer's disease |
ISSN: | 1387-2877 |
Popis: | 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 3.615.9%. 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 Alzheimers 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. Keywords |
Databáze: | OpenAIRE |
Externí odkaz: |