Apolipoprotein E (APOE) is a plasma protein and a central mediator of lipid (cholesterol and triglyceride) and lipoprotein metabolism. Its three isoforms E2, E3, and E4 (encoded by the alleles epsilon 2, 3 and 4, respectively) have been observed only in humans. In Western societies, APOE epsilon 4 is associated with increased morbidity and mortality, and represents a significant risk factor for age-related disorders such as atherosclerosis, cardiovascular events or late-onset Alzheimer's disease. The epsilon 4 allele occurs in approximately 14% of the general middle-aged German population. The greater disease risk of epsilon 4 carriers is generally attributed to elevated lipid levels but new evidence indicates that it may also be due to higher oxidative stress and pro-inflammatory states. APOE genotype-dependent effects may be differentially modulated by dietary factors.
This project aims at evaluating interactions on a molecular level between APOE genotype, dietary factors (e.g. caloric restriction) and ageing processes in gene targeted replacement mice applying so-called omics-techniques.
APOE targeted replacement mice expressing APOE4, APOE3 or APOE2 will be used as model for phenotypic characterization of APOE genotypes in response to different dietary treatments. Differential gene expression as well as biomarkers will be studied with special regard to traits associated with healthy ageing. Intestinal microbiome analysis may complete phenotypic characterization and help elucidate the interaction of APOE genotypes with dietary factors. Various omics‑techniques will complement molecular biology methods. In addition cell culture experiments using permanent cell lines including hepatocytes and macrophages transfected to express APOE isoforms aim to support the data obtained from targeted replacement mice.
Micro-CT, Foto: Anke Schlösser
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