We seek to understand neuronal senescence in the context of Alzheimer’s disease (AD). By combining studies in transgenic models of cerebral amyloidosis and human samples from cognitively normal subjects and AD patients, we are investigating molecular mechanisms that modulate cerebral amyloid metabolism, epigenetic landscape and neuronal bioenergetics. Our discoveries highlight the role of inflammation and dysbiosis in regulating gut-brain axis homeostasis. In collaboration with local neurologists, we conducted the first study of the contribution of rare and common genetic variants to AD susceptibility in a South American population. By focusing on unique factors that promote AD in older adults of Amerindian ancestry we will be able to better target prevention and treatment. Abnormal neuronal synaptogenesis and plasticity may partake in neurodegenerative disorders. Thus, another research aim in our lab focusses on elucidating the mechanisms involved in the regulation actin cytoskeleton.