Based on promising data from our pre-clinical research program, we propose two sequential clinical trials to test a new target and relevant repurposed medication for the treatment of Alzheimer's disease (AD). The new target is CYP46A1, the enzyme responsible for cholesterol elimination from the brain. The repurposed medication, efavirenz, is typically prescribed to decrease viral levels in HIV, but at much lower doses has been found to increase the activity of CYP46A1. In the first trial, we hope to identify the optimal dose of efavirenz that successfully activates CYP46A1 in subjects with normal cognition and early AD. In the second trial, we will enroll individuals across the spectrum of mild to moderate AD to test whether CYP46A1 activation (by efavirenz) reduces amyloid burden and leads to improvement in AD symptoms and disease progression. Based on its multiple mechanisms of action, efavirenz could function as both a disease-modifying medication as well as a symptomatic medication for the treatment of AD.