Murine models of Alzheimer's disease and their use in developing immunotherapies.
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 (sAbeta) peptide is converted into oligomeric/fibrillar Abeta. The oligomeric forms of Abeta are thought to be the most toxic, while fibrillar Abeta 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, Abeta 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.
Wisniewski
Thomas
T
Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. thomas.wisniewski@nyumc.org
Sigurdsson
Einar M
EM
D000544:Alzheimer Disease / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D051379:Mice
D023582:Alzheimer Vaccines
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