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.