Animal Models for candidate genes of Alzheimer’s disease

Coordinator:    Prof. Dr. Wolfgang Wurst
Institution: Institut für Entwicklungsgenetik, Helmholtz Zentrum München
For the past few years genes have been identified in genome-wide association studies which are involved in the development of Alzheimer’s disease (AD). Some of these genes are involved in the regulation of our fat metabolism, which is extremely interesting because there is increasing evidence of a correlation between nutrition and the risk of developing Alzheimer’s dementia. Therefore, in this subproject, the function of these novel candidate genes was investigated in genetic mouse mutants. In particular, a knock-out model for a gene involved in the metabolism of sphingolipids was established. This mouse model was fed on a specific type of feed to investigate a synergistic or protective effect of this environmental factor on the development of Alzheimer symptoms. Additionally, established transgenic AD-mouse models were incrossed to determine whether the genetic defect in the metabolism of sphingolipids still may increase Alzheimer symptoms. All mouse models were analysed in detail on the morphological, biochemical and behavioural level. In the first case, the development of distinct symptoms could indeed be reversed by a special diet in the mutant mice. In the second case, there are indications of a synergistic symptom modification. The results of this subproject contribute significantly to understand the pathogenesis of Alzheimer’s disease and thus contribute to the development of novel and better therapeutic strategies.
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