This Study Consists of Two Study Parts Conducted Under a Single IRB. Part I: Short Term ApoE-dependent Cerebral Blood Flow Response to Sirolimus in Cognitively Normal Adults Part II: Short Term ApoE-dependent Cerebral Blood Flow and Lung Perfusion Response to Sirolimus in Cognitively Normal Adults

This study consists of two study parts (Part I and Part II) conducted under a single IRB approval. Individuals that participated in Part I of the study were invited to participate in Part II of the study. Alzheimer's disease is a devastating neurodegenerative disease characterized by accumulation of clumps (also called plaques) and bundles of fibers (also called tangles) in the brain, for which there is currently no cure. Sirolimus is an FDA-approved medication which may improve the blood flow to the brain. Part I: This study is designed to see if sirolimus treatment improves MRI blood flow to the brain in individuals with and without a genetic predisposition to Alzheimer's disease. Part I of this study is complete and no longer enrolling participants. Part II: Ongoing research will expand the genetic predisposition cohort and further explore the drug's impact on the lung perfusion via hyperpolarized xenon-129 gas MRI and the brain-vascular connection. Only subjects who are APOE4 carriers will be enrolled in Part II. Hyperpolarized xenon-129 gas MRI is a non-invasive technique in which a subject inhales a bolus of hyperpolarized xenon-129 gas which can be directly imaged by the MRI as it physiologically distributes itself throughout the lung interior and within tissue and red blood cells. It thus allows for direct imaging and quantification of regional lung function: ventilation, gas-exchange, and perfusion. The relationship between pulmonary vascular function and brain perfusion is largely unstudied. We hope to investigate the relationship between pulmonary vascular function and cerebral blood flow by quantifying both lung and brain perfusion before and after the administration of Sirolimus.