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