Alzheimer's disease (AD) is the commonest neurodegenerative disease and, in recent years, studies have increasingly shown that vascular lesions are involved in the pathology of AD onset and progression. Many vascular changes precede the pathological changes and clinical symptoms of AD, and vascular lesions and AD have many common risk factors. Understanding the relationship between vascular factors and the pathological process of AD may help us to identify novel prevention and treatment strategies as well as delay disease progress. Previous studies have shown that lycopene has neuroprotective, antioxidant, and anticancer effects; however, the specific molecular mechanism mediating these effects remains unknown. In the present study, we found: 1) lycopene improved learning and memory in an AD mouse model; 2) lycopene inhibited amyloid plaque aggregation and neuroinflammation; and 3) lycopene induced LXR expression and activated the LXR-PI3K-AKT signaling pathway. Our findings suggest that promotion of neurogenesis and improvement of the functions of the neurovascular unit could be a novel direction for the development of AD therapies. (C) 2020 Published by Elsevier Inc.