The Alzheimer's Disease (AD) epidemic is a looming crisis, with an urgent need for new treatments to delay or prevent symptom onset and progression. Research in AD has identified changes in several potential biological markers which appear prior to the onset of memory loss, with some markers possibly changing one or two decades earlier. Since mild cognitive impairment (MCI) coincides with the onset of brain atrophy, this early stage of AD pathogenesis may offer a critical window of time to initiate novel therapies aimed at the events that lead to progressive neurodegeneration. This proposal seeks to apply concepts that have recently emerged from basic research in animal models of AD indicating that loss of the neurotransmitter norepinephrine (NE) causes inflammation and subsequent neuronal damage and reduces the clearance of Aß. Importantly, increasing NE reverses these effects and slows neuronal degeneration. The primary goal of this study is to provide evidence that treatment with atomoxetine achieves the intended mechanism of action, and specifically, will reduce levels of pro-inflammatory biomarkers in CSF. This proposal will test these concepts in humans for the first time and provide a foundation for future clinical trials to slow disease progression. Atomoxetine, a selective NE transport inhibitor, is an ideal drug to translate these findings to humans because it is already FDA-approved and safe in the elderly. The study will provide the essential next step to move this idea into an NIH funded multi-center clinical trial.