Nonhuman Primate Models of Alzheimer-Like Cerebral Proteopathy

Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Current pharmaceutical design (Impact Factor: 3.45). 01/2012; 18(8):1159-69. DOI: 10.2174/138161212799315885
Source: PubMed


Nonhuman primates are useful for the study of age-associated changes in the brain and behavior in a model that is biologically proximal to humans. The Aβ and tau proteins, two key players in the pathogenesis of Alzheimer's disease (AD), are highly homologous among primates. With age, all nonhuman primates analyzed to date develop senile (Aβ) plaques and cerebral β-amyloid angiopathy. In contrast, significant tauopathy is unusual in simians, and only humans manifest the profound tauopathy, neuronal degeneration and cognitive impairment that characterize Alzheimer's disease. Primates thus are somewhat paradoxical models of AD-like pathology; on the one hand, they are excellent models of normal aging and naturally occurring Aβ lesions, and they can be useful for testing diagnostic and therapeutic agents targeting aggregated forms of Aβ. On the other hand, the resistance of monkeys and apes to tauopathy and AD-related neurodegeneration, in the presence of substantial cerebral Aβ deposition, suggests that a comparative analysis of human and nonhuman primates could yield informative clues to the uniquely human predisposition to Alzheimer's disease.

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    • "Thus, modeling the full range of events of human aging-related diseases in any species, even in the most closely related to humans as other primates or in transgenic organisms expressing human disease-related genes, results extremely difficult if not impossi- ble. Despite all, several animal models have been generated and used in this context, from invertebrates such as Caenorhabditis elegans (Wolozin et al., 2011) or Drosophila melanogaster (Rincon-Limas et al., 2012; Thackray et al., 2014) to several primate species as marmosets or macaques (Heuer et al., 2012). Albeit the most widely developed and used models are indisputably transgenic mice. "
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    • "Another human-exclusive trait is the long period of healthy post-reproductive life of women, in stark contrast to other primates, which usually die before menopause (Walker and Herndon, 2008). Humans are also susceptible to such age-related diseases as Alzheimer's disease and Parkinson's disease, which are absent in all other primates (Finch and Austad, 2012; Heuer et al., 2012). Because this unique human aging phenotype emerged during the 6 million years since the human line diverged from that of the chimpanzee and bonobo, it must result from a relatively small number of genetic changes. "
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    • "Degeneration of serotonergic neurons was shown to be involved in the cognitive damage that accompanies A␤ cortical pathology. Primates are good models of normal aging and naturally occurring A␤ lesions, and they can be useful for testing diagnostic and therapeutic agents that target aggregated forms of A␤ that are similar to AD pathology [133] "
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