Format

Send to

Choose Destination
J Alzheimers Dis. 2017;55(1):159-170.

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

Author information

1
Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
2
Department of Neurodegeneration Diagnostics, Medical University of Białystok, and Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland.
3
AJ Roboscreen GmbH, Leipzig, Germany.
4
Paul Flechsig Institute of Brain Research, University of Leipzig, Germany.
5
Department of Neurosurgery, Universitätsklinikum Erlangen, and Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
6
Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, and Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
7
Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
8
Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
9
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
10
Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic, IDIBAPS, Barcelona, Spain.
11
Service of Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Switzerland.
12
Laboratory of Clinical Neurochemistry, Department of Medicine, Section of Neurology, University of Perugia, Perugia, Italy.
13
Hospices Civils de Lyon, Groupement Hospitalier Est, Biochemistry Department, Neurochemistry unit; Lyon University, Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR 5292, BioRaN Team, Bron Cedex, France.

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.

KEYWORDS:

Biomarkers; cerebrospinal fluid; phosphorylation; tau

PMID:
27662295
DOI:
10.3233/JAD-160448
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for IOS Press
Loading ...
Support Center