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

• DOI: 10.1016/j.neurobiolaging.2017.12.011
• Publication Date: 2017-12-20T04:48:16Z
• Authors: Paige E. Cramer; Renee C. Gentzel; Keith Q. Tanis; Joshua Vardigan; Yi Wang; Brett Connolly; Philip Manfre; Kenneth Lodge; John J. Renger; Celina Zerbinatti; Jason M. Uslaner
• Keywords: Male; 0301 basic medicine; Aging; Amyloid beta-Peptides; Prefrontal Cortex; Neurofibrillary Tangles; tau Proteins; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Cognition; Alzheimer Disease; Chlorocebus aethiops; Animals; Humans; Female

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.