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Alzheimer's disease (AD), the most common dementia in the elderly, is characterized by a relentless loss of higher cognitive function. With the rapid increase of the aging population, we face a burgeoning epidemic of AD. The number of people with Alzheimer's disease is predicted to triple in the next 50 years. Thus, there is an urgent need to further our understanding of AD pathogenesis and to identify novel therapeutic targets for prevention or treatment this devastating disease. Chronic peripheral and cerebral inflammation has emerged as one of the pathological hallmark of AD. A better understanding of specific molecular pathways in activated endothelial and glial cells may help designing preventative treatments for AD. In the AD brain, pro-inflammatory stimuli such as Advanced glycation endproducts (AGEs), beta-amyloid and dying neurons increase nitric oxide production by induction of the inducible nitric oxide synthase (iNOS) as well increase the expression of a variety of pro-inflammatory cytokines. We have shown that membrane permeable antioxidants including oestrogen derivatives (e.g. 17beta-oestradiol) thiol antioxidants (e.g. (R+)-alpha-lipoic acid), Gingko biloba extract EGb 761 and the polyphenols apigenin and resveratrol as well as fresh mushrooms and cinnamon prevent the up-regulation of these pro-inflammatory cytokines. As this pharmacological mechanism is not only relevant for Alzheimer's disease, but also for many chronic inflammatory conditions, such membrane-permeable antioxidants could be regarded not only as antioxidant, but also as potent therapeutic anti-inflammatory drugs for the prevention and treatment of AD.