Cellular and molecular mechanisms of neurodegeneration in Alzheimer's disease
Current projects relate to genetically modified mouse models of Alzheimer Disease, cholesterol metabolism. A particular focus is on Liver X Receptors (LXR). Their regulatory function in the brain in health and disease is being approached using complex transgenic mouse models of altered lipid metabolism. Behavioral phenotyping and histopathology are used to reveal clues of LXR controlled regulatory networks in brain. Age dependent and disease related changes in Immediate Early Genes (IEG) response to environmental factors, is the second major research theme. Molecular pharmacological and genetic approaches, gene profiling and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) in intact animal models of Alzheimer disease are being used to assess IEG controlled signaling pathways. AD pathogenesis in those models is assessed in the context of gene-environment interactions genome-wide using high-throughput genomic and epigenetic tools, diet and dietary manipulations.