Role of ABCG1 and ABCG4 in Abeta Generation in Brain

Project Summary

Recent studies suggest that cholesterol balance in the brain may affect development of Alzheimer's disease. Increased cholesterol is associated with increased risk of Alzheimer's disease while decreased cholesterol appears to reduce it. Recently, we have identified two membrane transporters that are involved in cholesterol transport in cells. These transporters are highly expressed in the brain. Now we have evidence suggesting that increased activity of these transporters enhances generation of Abeta, the molecule aberrant elevation and deposition of which is considered to be the major cause of Alzheimer's disease. Importantly, deficiency of the transporters appears to decrease Abeta production in the brain. ABCG4, one of two transporters, is mainly expressed in the brain and studies with mouse models of ABCG4 deficiency suggest that ABCG4 deficiency does not affect animal development and no impaired physiological functions have been identified in these mice. Therefore, ABCG4 may represent a novel drug target for treatment of Alzheimer's disease.