Multiple antioxidants in the prevention and treatment of Alzheimer disease: Analysis of biologic rationale

The etiology of Alzheimer disease (AD) is not well understood; therefore, n either prevention strategies nor long-term effective treatment modalities a re available for this disease. Based on laboratory and clinical studies, it appears that reactive oxygen species (ROS) and reactive nitrogen species ( RNS) that are generated extracellularly and intracellularly by various mech anisms are among the major intermediary risk factors that initiate and prom ote neurodegeneration in idiopathic AD. therefore, multiple antioxidant sup plements could be useful in the prevention of AD, and as an adjunct to stan dard therapy in the treatment of AD. The products of inflammatory reactions such as prostaglandins (PGs; PGE(1) and PGA(1)), free radicals, cytokines, and complement proteins are neurotoxic. Nonsteroidal antiinflammatory drug s (NSAIDs), which inhibit the synthesis of PGs, reduce the rate of deterior ation of cognitive functions in patients with advanced AD. Cholinergic drug s are routinely used in the treatment of AD to improve cognitive functions. Therefore, we propose that a combination of multiple antioxidants and NSAI Ds may be more beneficial in the prevention of AD, and that this combinatio n taken together with cholinergic drugs may be more effective in the treatm ent of AD than the individual agents alone. We also hypothesize that, in id iopathic AD, epigenetic components of neurons such as mitochondria. membran es, other membranous structures, and protein modifications-rather than the genes of neurons-are the primary targets for the action of neurotoxins incl uding free radicals. In some familial AD, mutations in amyloid precursor pr otein and presenilins are associated with the risk of early onset of this d isease; however, their mechanisms of action are not fully understood.