期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 40, 期 -, 页码 S135-S145出版社
IOS PRESS
DOI: 10.3233/JAD-132237
关键词
Alzheimer's disease; neurofibrillary tangles; paired helical filaments-tau; tau vaccination
资金
- Diane program (Walloon region) [816856]
- Fonds de la Recherche Scientifique Medicale and performed in the frame of the Interuniversity Attraction Poles program of the Belgian Federal Science Policy Office - program Investissements d'avenir [3.4504.10, P7/16, ANR-11-INBS-0011]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据