Project Summary Alzheimer’s disease (AD) is a major health concern defined by pathologic changes in the brain that coincide with altered behavior and cognitive function. Many have suggested that there is a need for primate models of AD because they naturally recapitulate some neuropathological features of AD with advanced age whereas other model organisms (i.e., rodents) do not. For instance, while amyloid-beta (Aβ) deposition occurs in most mammals, tau-positive neurofibrillary tangles (NFT) have only been identified in a few nonhuman species studied to date. Additionally, elderly nonhuman primates from several different Genera, develop cerebral amyloid angiopathy (CAA), a neurovascular condition found in 80% of AD patients and associated with cognitive decline. Here, we are proposing to develop squirrel monkeys as a model species for current and future studies on the biology of aging and AD research. Specifically, we propose to train a cohort of group socially-living squirrel monkeys on the use of an automated cognitive testing system (ACTS) that is designed to assess a variety of cognitive functions including learning, memory and executive control. Creating large cohorts of squirrel monkeys trained on the ACTS system will provide animals with established cognitive phenotypes for use in preclinical studies and allow for examining their association with potential age-related differences in neuroanatomical, neuropathological and biomarker data. In addition, we will test whether experience with an ACTS influences age-related changes in gray matter volume and white matter integrity. Magnetic resonance images (MRI) will be obtained from 20 elderly and geriatric monkeys trained on the ACTS and 20 age-sex matched control monkeys that were not trained on the ACTS. To examine whether learning to use an ACTS slows down the normal brain aging process, we will compare gray matter volume and white matter integrity between the ACTS and control monkeys using voxel-based morphometry. If cognitive stimulation late in life preserves cognitive functioning and inhibits rates of change in cortical organization, then we hypothesize that ACTS monkeys will have increased gray matter volume and white matter integrity in brain regions sensitive to aging. The proposed studies, in their entirety, will fill an important gap in our knowledge about the comparative biology of aging and cognition in squirrel monkeys and will also create an invaluable nonhuman primate resource for future use preclinical studies.

Projective Narrative Alzheimer’s disease (AD) and age-associated neurodegenerative disorders are a major public health concern. The proposed studies aim to further develop squirrel monkeys as a model species for studies on cognitive aging and their potential associations with neurological and pathological changes in the central nervous system. Further development of primate models for studies on AD pathology and related dementias will provide new and alternative avenues of therapeutic interventions and increased translational value.