Drug Discovery

Anti-amyloid

Estrogen and ApoE; Interaction and effect on Pathogenesis in a Mouse Model of Alzheimer's Disease

Investigator(s): Jonathan D. Smith, Ph.D., Associate Professor

Institution(s): Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY

Duration: 1999 - 2001

Summary:

Apolipoprotein E (apoE) plays a role in the reparative response of the brain after injury. People, particularly women, with the E4 allele are at higher risk of developing AD. The relationship between estrogen, apoE and AD is not clear. Using transgenic mouse models of AD, estrogen receptor and apoE knockout mice, investigators will evaluate the effects of estrogens on amyloid deposition in mice with differing apoE genotypes. Other studies will determine whether the protective effects of estrogens occur via genomic or nongenomic mechanisms. New forms of estrogen will also be evaluated in this project. This project should answer a number of questions regarding the protective effects of estrogen and will help develop more rational drug discovery for new, more effective estrogen analogues to treat AD.