Evaluating the protective effect of a TSPO ligand in Alzheimer’s disease mouse model

Alzheimer’s disease (AD) is the most common cause of dementia in the world, predicted to be
affecting over 55 million people globally. Its main clinical features are short-term memory loss,
impaired learning, visual and spatial awareness disturbances and poor executive functions. One
of the main causes of developing AD is abnormal accumulation of a type of protein called amyloid
beta (Aβ) in the brain. Previous studies demonstrated that increased level of cholesterol is
associated with the growth of Aβ and worsening of AD symptoms. Our recent data has shown a
protein, called TSPO, mediates cholesterol removal in the retina, a part of central nervous
system. Another small chemical, named Etifoxine, can activate TSPO, promoting cholesterol
removal in the retina. Treatment with Etifoxine resulted in significantly decreased levels of
cholesterol in the serum and retina of high-fat-diet-fed mice, when compared to that of high-fatdiet-fed mice without Etifoxine treatment. This project will examine whether Etifoxine can lower
cholesterol in the brain and slow disease progression in an AD mouse model.