Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 290, Issue 7, Pages 4059-4074Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.627919
Keywords
-
Categories
Funding
- Research Foundation Flanders (FWO-Vlaanderen)
- KU Leuven Research Fund (KU Leuven-BOF)
- KU Leuven Research Fund (KU Leuven-IOF)
- KU Leuven RD
- Agency for Innovation by Science and Technology (IWT)
- IWT Ph.D. fellowship
- FWO-Vlaanderen postdoctoral fellowships
- LabEx DISTALZ (Excellent Laboratory-Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease)
- CNRS Large Scale Facility NMR THC [Fr3050]
- INSERM
- CNRS
- University of Lille 2
- Lille Metropole Communaute Urbaine (LMCU)
- Region Nord/Pas-de-Calais
- FEDER
- University of Antwerp Research Fund
- Alzheimer Research Foundation (SAO-FRA)
- central Biobank facility of the Institute Born-Bunge/University Antwerp
- Belgian Science Policy Office Interuniversity Attraction Poles (IAP) program
- Flemish Government
Ask authors/readers for more resources
A link between Tau phosphorylation and aggregation has been shown in different models for Alzheimer disease, including yeast. We used human Tau purified from yeast models to generate new monoclonal antibodies, of which three were further characterized. The first antibody, ADx201, binds the Tau proline-rich region independently of the phosphorylation status, whereas the second, ADx215, detects an epitope formed by the Tau N terminus when Tau is not phosphorylated at Tyr(18). For the third antibody, ADx210, the binding site could not be deter-mined because its epitope is probably conformational. All three antibodies stained tangle-like structures in different brain sections of THY-Tau22 transgenic mice and Alzheimer patients, and ADx201 and ADx210 also detected neuritic plaques in the cortex of the patient brains. In hippocampal homogenates from THY-Tau22 mice and cortex homogenates obtained from Alzheimer patients, ADx215 consistently stained specific low order Tau oligomers in diseased brain, which in size correspond to Tau dimers. ADx201 and ADx210 additionally reacted to higher order Tau oligomers and presumed prefibrillar structures in the patient samples. Our data further suggest that formation of the low order Tau oligomers marks an early disease stage that is initiated by Tau phosphorylation at N-terminal sites. Formation of higher order oligomers appears to require additional phosphorylation in the C terminus of Tau. When used to assess Tau levels in human cerebrospinal fluid, the antibodies permitted us to discriminate patients with Alzheimer disease or other dementia like vascular dementia, indicative that these antibodies hold promising diagnostic potential.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available