The Influence of Life-Style Change and APOE Gene in Aging and AD

The goal of this proposal is to investigate how diet control or exercise affects brain health using animal models with aging or Alzheimer’s disease, and with or without the APOE4 gene. Using animal models carrying different APOE genes, we will change their life-style during aging (in Aim 1) or during the development of Alzheimer’s disease (in Aim 2). These life-style changes include controlled diet, high-fat-diet, and exercise. We will evaluate the brain health and pathology under different treatment, using complex biological big data to find novel associations among life-style change, APOE gene, aging, and Alzheimer’s disease.

Heterogeneity in humans due to genetic diversity and the impact of many environmental differences limits the molecular study of disease mechanisms. However, mouse models offer opportunities to study the effects of disease-related risk factors in a relatively pure genetic background within a controlled environment. Therefore, our proposal is innovative to address how APOE gene impacts life-style change in healthy aging and Alzheimer’s disease by using animal models expressing human APOE genes. Our study will aid to fill the gaps in knowledge regarding how life-style change affects the brain, and how APOE gene further influences this effect. Ultimately, our study will provide guidance for designing APOE gene-specific strategies to prevent or delay aging and Alzheimer’s disease.

Heterogeneity in humans due to genetic diversity and the impact of many environmental differences limits the molecular study of disease mechanisms. However, mouse models offer opportunities to study the effects of disease-related risk factors in a relatively pure genetic background within a controlled environment. Therefore, our proposal is innovative to address how APOE gene impacts life-style change in healthy aging and Alzheimer’s disease by using animal models expressing human APOE genes.

Our study will aid to fill the gaps in knowledge regarding how life-style change affects the brain, and how APOE gene further influences this effect. Ultimately, our study will provide guidance for designing APOE gene-specific strategies to prevent or delay aging and Alzheimer’s disease.