Murine models of Alzheimer's disease and their use in developing immunotherapies

作者：Wisniewski Thomas^*; Sigurdsson Einar M

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2010, 1802(10): 847-859.

DOI：10.1016/j.bbadis.2010.05.004

• Transgenic mice
• Amyloid beta
• Congophilic angiopathy
• tau
• Immunization
• Neurofibrillary tangles
• lmmunomodulation
• Alzheimer's disease

Alzheimer's disease (AD) is one of the categories of neurodegenerative diseases characterized by a conformational change of a normal protein into a pathological conformer with a high beta-sheet content that renders it resistant to degradation and neurotoxic. In AD, the normal soluble amyloid beta (sA beta) peptide is converted into oligomeric/fibrillar A beta. The oligomeric forms of A beta are thought to be the most toxic, while fibrillar A beta, becomes deposited as amyloid plaques and congophilic angiopathy, which both serve as neuropathological markers of the disease. An additional important feature of AD is the accumulation of abnormally phosphorylated tau as soluble toxic oligomers and as neurofibrillary tangles. 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 specific aspects of AD pathology. None of the current murine models is a perfect match of the human disease. Perhaps the most exciting of the therapeutic approaches being developed is immunomodulation targeting the aggregating proteins, A beta and tau. This type of AD therapy is currently being assessed in many transgenic mouse models, and promising findings have led to clinical trials. However, there is a discrepancy between results in murine models and ongoing clinical trials, which highlight the limitations of these models and also of our understanding of the underlying etiology and pathogenesis of AD. Because of these uncertainties, Tg models for AD are continuously being refined with the aim to better understand the disease and to enhance the predictive validity of potential treatments such as immunotherapies.

• 出版日期2010-10