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Aged primate
Because of their permanent overexpression and the phylogenetic distance between rodents and primates, results obtained with transgenic mice may be unrelevant for humans. As a consequence, we lack an appropriate, spontaneous model to test whether the development of the pathognomonic lesions of AD are directly correlated with the cognitive changes observed during the disease.
Monkeys might be considered as the ideal natural models because of their phylogenic proximity to humans. However, their weight, size, cost, and lifespan preclude their use them as laboratory models. By contrast, we explore the potential of the lemur Microcebus murinus to be used as a natural primate model of AD.
 View all comments by Jean-Michel VERDIER |
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For studying β-secretase APP processing, we use the guinea pig model. We like that model, in part, because the β-secretase processing closely mimics that which occurs in Alzheimer disease patients. Specifically, the guinea pig has an APP β-secretase cleavage sequence identical to the human wild-type sequence, the type found in 99 percent of AD patients. Thus, for developing β-secretase inhibitors, the guinea pig is a good model because the β-secretase processing is that which occurs in the vast majority of patients.
In contrast, we believe that the more popular transgenic Swedish APP mouse model is not suitable for developing β-secretase inhibitors. That model contains a mutated APP β-secretase cleavage sequence, which occurs in only one family. That mutated APP completely alters the β-secretase processing from that which occurs in wild-type APP β-secretase processing. Thus, β-secretase inhibitors developed in this model are likely to be ineffective for treating most AD patients.
References:
Beck M, Bigl V, Rossner S. Guinea pigs as a nontransgenic model for APP processing in vitro and in vivo.
Neurochem Res. 2003 Apr;28(3-4):637-44. Review.
Abstract
View all comments by Greg Hook |
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