A Novel Role of ApoA-I in Alzheimer's Disease

Emerging evidence indicates that Alzheimer’s disease and cardiovascular disease share common risk factors and pathogenic mechanisms. Human apoA-I is a major cardio-protective protein but its role in the brain pertinent to Alzheimer’s disease has not been defined. This study will use a combination of behavioral, biochemical, and electrophysiological approaches to investigate the role of human apoA-I in the development of Alzheimer’s disease-like behavior and neuropathology in a mouse model of Alzheimer’s disease.

To date, there is no cure for Alzheimer’s disease. Emerging evidence indicates that Alzheimer’s disease and heart disease are closely connected and may respond to common therapies. Human apolipoprotein (apo) A-I is a major heart-protective protein but its role in the brain pertinent to Alzheimer’s disease has not been studied thoroughly. Several lines of evidence suggest that human apoA-I may have anti-Alzheimer’s disease effects. However, the underlying mechanisms for such effects are not clear. This research project will address this issue by investigating the potential role of human apoA-I in the development of Alzheimer’s disease-like symptoms in an animal model of Alzheimer’s disease. The researchers will use genetically modified mice that carry human genes with Alzheimer’s disease mutations and develop memory deficits and brain lesions during aging. By breeding the Alzheimer’s disease mice with mice carrying the gene for human apoA-I, the researchers will produce Alzheimer’s disease mice with a high level of human apoA-I in the blood circulation. With these mice, the researchers will: 1) determine the effects of human apoA-I on Alzheimer’s disease-like symptoms at different stages of disease development and 2) determine the direct effect of human apoA-I on the properties of neuronal cells responsible for memory formation and storage. Results from these studies will not only provide insights into the biological role of apoA-I in the brain but also may lead to the development of novel therapies for fighting against Alzheimer’s disease.