Our research program focuses on the synaptic and cellular basis of cognitive decline in rhesus monkeys. We have identified several reflections of synaptic health that deteriorate with aging, leading to cognitive decline. A key question being pursued is whether or not such synaptic alterations can transition to the neurodegenerative events seen in Alzheimer’s Disease (AD) under certain circumstances. In order to pursue this question in the Rhesus monkey model, we have developed two monkey models of early AD, one based on the synaptic toxicity of AB oligomers, and one based on the capacity for phospho-tau aggregates to initiate neurodegeneration. Both models show great promise and are currently being pursued in the laboratory. We are also pursuing other models of cognitive decline as well that have a high degree of translational impact on human health, (e.g. HIV-associated neurocognitive decline).