title: Risk factors for Alzheimer's disease: role of multiple antioxidants, non-steroidal anti-inflammatory and cholinergic agents alone or in combination in prevention and treatment.
abstract: The etiology of Alzheimer's disease (AD) is not well understood. Etiologic factors, chronic inflammatory reactions, oxidative and nitrosylative stresses and high cholesterol levels are thought to be important for initiating and promoting neurodegenerative changes commonly found in AD brains. Even in familial AD, oxidative stress plays an important role in the early onset of the disease. Mitochondrial damage and proteasome inhibition represent early events in the pathogenesis of AD, whereas increased processing of amyloid precursor protein (APP) to beta-amyloid (Abeta) fragments (Abeta(40) and Abeta(42)) and formation of senile plaques and neurofibrillary tangles (NFTs) represent late events. We propose a hypothesis that in idiopathic AD, epigenetic components of neurons such as mitochondria, proteasomes and post-translation protein modifications (processing of amyloid precursor protein to beta-amyloid and hyperphosphorylation of tau), rather than nuclear genes, are the primary targets for the action of diverse groups of neurotoxins. Based on epidemiologic, laboratory and limited clinical studies, we propose that a combination of non steroidal anti-inflammatory drugs (NSAIDs) and appropriate levels and types of multiple micronutrients, including antioxidants, may be more effective than the individual agents in the prevention, and they, in combination with a cholinergic agent, may be more effective in the treatment of AD than the individual agents alone. In addition, agents, which can prevent formation of plaques or dissolve these plaques may further enhance the efficacy of our proposed treatment strategy.
authors.affiliation: Center for Vitamins and Cancer Research, Department of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Kedar.Prasad@UCHSC.edu
authors.forename: Kedar N
authors.initials: KN
authors.lastname: Prasad
authors.forename: William C
authors.initials: WC
authors.lastname: Cole
authors.forename: K Che
authors.initials: KC
authors.lastname: Prasad
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018678:Cholinergic Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D018384:Oxidative Stress; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018678:Cholinergic Agents