Aging African green monkeys manifest transcriptional, pathological, and cognitive hallmarks of human Alzheimer's disease
| Autor: | Yi Wang, Renee C Gentzel, Paige Cramer, Philip Manfre, Celina Zerbinatti, Kenneth Lodge, Jason M. Uslaner, Keith Q. Tanis, Joshua D. Vardigan, Brett Connolly, John J. Renger |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Aging Amyloid beta Prefrontal Cortex tau Proteins Disease 03 medical and health sciences 0302 clinical medicine Cognition Alzheimer Disease Chlorocebus aethiops medicine Animals Humans Pathological Amyloid beta-Peptides biology business.industry General Neuroscience Neurofibrillary Tangles biology.organism_classification Dorsolateral prefrontal cortex Rhesus macaque Disease Models Animal 030104 developmental biology Visual cortex medicine.anatomical_structure biology.protein Female Neurology (clinical) African Green Monkey Geriatrics and Gerontology business Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of aging. 64 |
| ISSN: | 1558-1497 |
| Popis: | While many preclinical models of Alzheimer's disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in 2 higher order species, the African green monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans. Biochemically, age-related changes in AGM cerebrospinal fluid levels of tau, phospho-tau, and amyloid beta were consistent with AD. Histologically, aged AGMs displayed pathological hallmarks of the disease, plaques, and 2 AGMs showed evidence of neurofibrillary tangle-like structures. We hypothesized and confirmed that AGMs have age-related cognitive deficits via a prefrontal cortex-dependent cognition test, and that symptomatic treatments that improve cognition in AD patients show efficacy in AGMs. These data suggest that the AGM could represent a novel and improved translational model to assist in the development of therapeutics for AD. |
| Databáze: | OpenAIRE |
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