The aim of the project is to develop a safe and nutraceutical-like formulation of UbisolQ10 (UQ), a unique water-soluble formula in combination with water-soluble Ashwagandha extract (AE), that can arrest the progression of Alzheimer’s Disease (AD). This novel formulation significantly increases bioavailability of CoQ10 and other compounds in the brain. This combinatorial treatment can target multiple mechanisms implicated in AD development including mitochondrial dysfunction, oxidative stress, inflammation and dysregulation of autophagy. Efficacy of water-solubilized formulation of lipophilic compounds will be evaluated, AE and Ubisol-Q10, in halting the progression of AD in double and triple transgenic mouse models of AD. Neuroprotective abilities of AE and UQ separately and in combination will be determined and behavioral analyses of long-term, short-term or working memories of animals in treatment and control groups will be conducted. Pathological features, including abnormal ?-amyloid plagues, cell death and autophagy markers, and astroglia response will be also assessed by immunohistochemical methods. Results of this project will lead to a potential therapeutic and preventative treatment for AD.