The Contribution of Transgenic Models to the Understanding of Alzheimer's Disease Progression and Therapeutic Development
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Published:24 May 2011
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Special Collection: 2011 ebook collection , 2011 ebook collection , 2011-2015 industrial and pharmaceutical chemistry subject collectionSeries: Drug Discovery Series
M. A. Chabrier, K. M. Neely, N. A. Castello, and F. M. LaFerla, in Animal Models for Neurodegenerative Disease, ed. J. Avila, J. J. Lucas, and F. Hernandez, The Royal Society of Chemistry, 2011, pp. 1-14.
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Transgenic mouse models of Alzheimer disease (AD) have been invaluable in unraveling the mechanisms of disease progression and for testing potential therapeutic interventions. Since the cause of sporadic AD is unknown, transgenic models of AD are primarily based on mutations found only in patients with familial AD. These mutations produce pathological and cognitive changes that resemble sporadic AD, and thus these transgenic mice are still extremely useful for studying this more common form of AD. Here we discuss notable advances in our understanding of AD pathogenesis that have directly resulted from studies with transgenic models of AD, such as the finding from 3xTg-AD mice and other models demonstrating that tau pathology is facilitated by amyloid-beta. We also discuss several promising therapeutics that were largely characterized using transgenic mice, including immunotherapy, HDAC inhibitors, and M1 receptor agonists.