To prevent and treat age associated neurodegenerative diseases is a key challenge of this century. Based on recent findings it is promising to develop dietary lipid related disease prevention strategies. The present project will undertake this strategic approach which will first be applied to Alzheimer's disease, in which brain lipids are believed to play an important role. Three converging lines of investigation will be pursued. In vitro studies of the role of lipids in neuronal degeneration and of the effects thereon of distinct lipid related treatments will be preformed first. The resulting promising treatments will than be used for the preparation of formulations whose effectiveness will be tested in vivo utilising distinct models of neurodegeneration and dementia. The best diets will be tested in man for their ability to halt and prevent disease.
The objective of this proposal is to develop and evaluate lipid diets and related food additives for their preventive and treatment-related beneficial effects on age related brain neurodegeneration and Alzheimer disease (AD). This will be done by experiments directed at this complementary and interrelated lines of investigation:
- Cellular and molecular studies of the role of lipids in brain neurodegeneration and effects of distinct lipid related treatments on neuronal function;
- Formulation of promising lipid related treatments and assessment, utilising in vivo models of brain neurodegeneration and AD, of their bioavailability and effectiveness;
- Lipid diet studies in man, to slow down and eventually prevent disease. The chronic nature of neurodegeneration and bioavailibility render this lipid diet approach particularly promising.
Lipid modulation of APP, Aß and PS processing. Epidemiological results on early cholesterol levels, dietary habits for later in life diseases, pharmacokinetics of 20 lipid treatments, electrophysiology, 5 diets for in vivo use with preventive potential, ApoE3 and ApoE4 effects, in vivo effects, safety, influence on peripheral lipid metabolism, neurological preventive diet, dietary advice.