Immunotherapeutic approaches for Alzheimer’s disease in transgenic mouse models

被引：0
作者：
Thomas Wisniewski
Allal Boutajangout
机构：
[1] New York University School of Medicine,Department of Neurology
[2] New York University School of Medicine,Department of Pathology
[3] New York University School of Medicine,Department of Psychiatry, Millhauser Laboratory
来源：
Brain Structure and Function | 2010年 / 214卷
关键词：
Transgenic mice; Amyloid β; Congophilic angiopathy; Tau; Vaccination; Immunomodulation; Alzheimer’s disease;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Alzheimer’s disease (AD) is a member of a category of neurodegenerative diseases characterized by the conformational change of a normal protein into a pathological conformer with a high β-sheet content that renders it resistant to degradation and neurotoxic. In the case of AD the normal soluble amyloid β (sAβ) peptide is converted into oligomeric/fibrillar Aβ. The oligomeric forms of Aβ are thought to be the most toxic, while fibrillar Aβ becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. In addition, the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles is an essential part of the pathology. Many therapeutic interventions are under investigation to prevent and treat AD. The testing of these diverse approaches to ameliorate AD pathology has been made possible by the existence of numerous transgenic mouse models which each mirror different aspects of AD pathology. Perhaps the most exciting of these approaches is immunomodulation. Vaccination is currently being tried for a range of age associated CNS disorders with great success being reported in many transgenic mouse models. However, there is a discrepancy between these results and current human clinical trials which highlights the limitations of current models and also uncertainties in our understanding of the underlying pathogenesis of AD. No current AD Tg mouse model exactly reflects all aspects of the human disease. Since the underlying etiology of sporadic AD is unknown, the process of creating better Tg models is in constant evolution. This is an essential goal since it will be necessary to develop therapeutic approaches which will be highly effective in humans.
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页码：201 / 218
页数：17
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