Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Diane Jansen (Donders Series 133)

25 November 2013

Promotors: Prof.dr. C.A.M. Gielen, Prof.dr. A. Heerschap

Copromotor: dr. A. J. Kiliaan

The role of nutrition in Alzheimer's disease - a study in transgenic mouse models for Alzheimer's disease and vascular disorders

Recently, many epidemiological studies have shown that vascular disorders, such as hypertension, hypercholesterolemia and atherosclerosis, are major risk factors for Alzheimer’s disease (AD). Modification of these vascular-based risk factors by means of changing lifestyle, such as nutritional intake, can alter the risk of developing AD later in life. While dietary intake of typical Western diets (TWD), high in saturated fatty acids such as cholesterol, increases the incidence of cardiovascular disease and AD, adherence to a Mediterrean diet, rich in omega-3 long-chain polyunsaturated fatty acids (n3 lc-PUFAs), vitamins and antioxidants, lowers the incidence of vascular disorders and reduces the risk of developing AD later in life. The studies reported in my thesis aimed to provide more insight into the longitudinal etiopathogenic processes contributing to AD and to understand how nutrition may affect AD development, with an emphasis on behavioral and cognitive testing, proton magnetic  resonance spectroscopy (1H MRS) at 7 and 11.7 Tesla, and neuropathology. To address these issues, three distinct transgenic mouse models were used. The double transgenic AβPPswe-PS1dE9 mouse model represents a model for familial early-onset AD. The human apolipoprotein E ε4/ε4 carrier (apoE4) and the apolipoprotein (apoE) knockout (B6, 129P-Apoetm1Unc/J) mouse models represent models for vascular disorders. Unraveling the exact mechanisms by which dietary nutrients influence AD pathogenesis is necessary for the development of effective nutritional (preventative) interventions.