Aging African green monkeys manifest transcriptional, pathological, and cognitive hallmarks of human Alzheimer's disease

• Published in: Neurobiology of aging Vol. 64; pp. 92 - 106
• Main Authors: Cramer, Paige E., Gentzel, Renee C., Tanis, Keith Q., Vardigan, Joshua, Wang, Yi, Connolly, Brett, Manfre, Philip, Lodge, Kenneth, Renger, John J., Zerbinatti, Celina, Uslaner, Jason M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2018
• Subjects: African green monkey; Alzheimer's disease; Amyloid beta; Cognition; Rhesus; Tau; Tau; Cognition; Amyloid beta; Rhesus; African green monkey; Alzheimer's disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2017.12.011

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.