Apolipoprotein E genotype, vitamin E, and Alzheimer's disease prevention

Alzheimer's disease (AD) is a multi-causal neurodegenerative disorder and the most common form of dementia in the elderly. Although extensively investigated, the exact underlying molecular and cellular mechanisms of AD remain to be fully elucidated. Amongst other factors, AD may be associated with increased oxidative stress and chronic inflammation. Although dietary antioxidants, in particular vitamin E, have been related to a reduction of AD risk, data from clinical studies are still contradictory, Aside from increasing age, one key risk factor for sporadic AD is the apolipoprotein E4 genotype. As major component of lipoproteins the apolipoprotein E (apoE) is of crucial importance in the distribution of cholesterol and lipids within the brain and thus, involved in neuronal membrane repair mechanisms. However, apoE4 has been associated with several altered cellular features including an impaired neuronal repair function and a higher neuronal vulnerability towards oxidative insults leading to an increased AD risk. In this context, the role of antioxidant supplementation as a primary prevention strategy for subjects at high risk including carriers of the apo epsilon 4 allele, is discussed.