Genetic Control of Amyloid Precursor Protein Processing

Clinical and neurological studies suggest that human Alzheimer’s disease (AD) is highly variable in terms of the length, severity and age-related progression of the disease. Accumulating evidence suggests that its development and progression is subject to a variety of environmental and genetic influences. Studies have shown that early-onset familial AD may be caused by mutations in various AD genes. These genetic forms of AD all share a common pathology that involves alterations in the processing and metabolism of the amyloid beta peptide (Aß). The release of Aß from its precursor and the production, transport, turnover and deposition of Aß in the brain is still unclear. Dr. Lamb is focusing on a unique animal model for AD with entire copies of human AD genes placed in mice. These “genomic-based” transgenic animals will be used to study the processing and metabolism of Aß in mice with different genetic backgrounds. The long-term goal of this proposal is to complement genetic studies in humans to identify novel genetic pathways involved in the modulation of Aß processing and metabolism.

Grantee institution at the time of this Grant: The Cleveland Clinic Foundation