Vaccination with Sarkosyl insoluble PHF-tau decrease neurofibrillary tangles formation in aged tau transgenic mouse model: a pilot study
| Autor: | Robert Dedecker, Jean Pierre Brion, Anna Kabova, Michèle Authelet, Céline Heraud, Valérie Suain, Karelle Leroy, Christelle Frédérick, Virginie Stygelbout, Marie-Claude Potier, Charles Duyckaerts, Zehra Yilmaz, Kunie Ando |
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| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Mutant Mice Transgenic Pilot Projects tau Proteins Biology Hippocampal formation Active immunization Mice Alzheimer Disease mental disorders medicine Animals Humans Aged 80 and over Neurons General Neuroscience Vaccination Brain Neurofibrillary Tangles Sarcosine General Medicine medicine.disease Molecular biology Psychiatry and Mental health Clinical Psychology Titer Disease Models Animal Immunization biology.protein Female Tauopathy Geriatrics and Gerontology Antibody |
| Zdroj: | Journal of Alzheimer's disease : JAD. 40 |
| ISSN: | 1875-8908 |
| Popis: | Active immunization using tau phospho-peptides in tauopathy mouse models has been observed to reduce tau pathology, especially when given prior to the onset of pathology. Since tau aggregates in these models and in human tauopathies are composed of full-length tau with many post-translational modifications, and are composed of several tau isoforms in many of them, pathological tau proteins bearing all these post-translational modifications might prove to be optimal tau conformers to use as immunogens, especially in models with advanced tau pathology. To this aim, we immunized aged wild-type and mutant tau mice with preparations containing human paired helical filaments (PHF) emulsified in Alum-adjuvant. This immunization protocol with fibrillar PHF-tau was well tolerated and did not induce an inflammatory reaction in the brain or adverse effect in these aged mice. Mice immunized with four repeated injections developed anti-PHF-tau antibodies with rising titers that labeled human neurofibrillary tangles in situ. Immunized mutant tau mice had a lower density of hippocampal Gallyas-positive neurons. Brain levels of Sarkosyl-insoluble tau were also reduced in immunized mice. These results indicate that an immunization protocol using fibrillar PHF-tau proteins is an efficient and tolerated approach to reduce tau pathology in an aged tauopathy animal model. |
| Databáze: | OpenAIRE |
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