Anti-β-sheet conformation monoclonal antibody reduces tau and Aβ oligomer pathology in an Alzheimer's disease model
| العنوان: | Anti-β-sheet conformation monoclonal antibody reduces tau and Aβ oligomer pathology in an Alzheimer's disease model |
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| المؤلفون: | Allal Boutajangout, Pankaj Mehta, Mitchell Marta-Ariza, Frances Prelli, Daniel Peyser, Krystal Herline, Thomas Wisniewski, Eleanor Drummond, Fernando Goni |
| المصدر: | Alzheimer's Research & Therapy Alzheimer’s Research & Therapy, Vol 10, Iss 1, Pp 1-16 (2018) |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, medicine.medical_specialty, medicine.drug_class, Cognitive Neuroscience, Mice, Transgenic, tau Proteins, Disease, Motor Activity, Monoclonal antibody, Oligomer, lcsh:RC346-429, lcsh:RC321-571, Pathogenesis, Immunomodulation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alzheimer Disease, Extracellular, medicine, Animals, Humans, Immunologic Factors, Amyloid-β, Maze Learning, Protein secondary structure, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Radial arm maze, Amyloid beta-Peptides, Chemistry, Research, Brain, 3. Good health, Dissociation constant, Disease Models, Animal, 030104 developmental biology, Neurology, Immunoglobulin M, Oligomers, Prion, Protein Conformation, beta-Strand, Neurology (clinical), Tau, 030217 neurology & neurosurgery |
| الوصف: | Background Oligomeric forms of amyloid-β (Aβ) and tau are increasing being recognized as key toxins in the pathogenesis of Alzheimer’s disease (AD). Methods We developed a novel monoclonal antibody (mAb), GW-23B7, that recognizes β-sheet secondary structure on pathological oligomers of neurodegenerative diseases. Results The pentameric immunoglobulin M kappa chain (IgMκp) we developed specifically distinguishes intra- and extracellular pathology in human AD brains. Purified GW-23B7 showed a dissociation constant in the nanomolar range for oligomeric Aβ and did not bind monomeric Aβ. In enzyme-linked immunosorbent assays, it recognized oligomeric forms of both Aβ and hyperphosphorylated tau. Aged triple-transgenic AD mice with both Aβ and tau pathology infused intraperitoneally for 2 months showed IgMκp in the soluble brain homogenate, peaking at 24 h postinoculation. Treated mice exhibited significant cognitive rescue on radial arm maze testing compared with vehicle control-infused mice. Immunohistochemically, treatment resulted in a significant decrease of extracellular pathology. Biochemically, treatment resulted in significant reductions of oligomeric forms of Aβ and tau. Conclusions These results suggest that GW-23B7, an anti-β-sheet conformational mAb humanized for clinical trials, may be an effective therapeutic agent for human AD. Electronic supplementary material The online version of this article (10.1186/s13195-018-0337-3) contains supplementary material, which is available to authorized users. |
| تدمد: | 1758-9193 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::81a2f8ae241f7bd32db090627775021b https://pubmed.ncbi.nlm.nih.gov/29378642 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....81a2f8ae241f7bd32db090627775021b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17589193 |
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