الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Alzheimer disease (AD) is the most common neurodegenerative disorder of the elderly. Its heterogeneous etiology makes it difficult to define clinically the most important factor in determining the onset and progression of the disease.
Many hypotheses have been raised regarding the pathophysiology of AD. The most common is the amyloid hypothesis. The amyloid hypothesis emphasizes that increased β amyloid production or failure of its clearance induce gradual β amyloid accumulation throughout life, resulting in the formation of amyloid plaques, which induce oxidative stress and inflammatory responses resulting in synaptic damage, tau tangles, and then neuronal loss. The resulting oxidative stress and inflammation are characterized by the release of cytokines and reactive oxygen species known to activate the nuclear factor-kappa β (NF- κB) which further activates inflammatory processes. In addition, β amyloid levels in brain are influenced not only by its production, but also by different clearance mechanisms including its clearance to blood and CSF, phagocytosis by microglia, and enzymatic degradation. Neprilysin (NEP) is one of the most important β amyloid degrading enzymes whose levels were found to decrease in AD.
There is currently no cure for AD; however, there are multiple drugs that have been proven to treat symptoms of AD. Investigations for novel therapeutic approaches targeting the presumed underlying pathogenic mechanisms are a major research focus. Antiamyloid agents and tau-related therapies are under clinical trials. In addition to pharmaceutical agents, attention has recently been directed towards the role of other therapeutic adjuncts including exercise and diet control. There are studies showing that exercise decreases the risk of neurodegenerative disease such as AD. Moreover, high fat diet (HFD) was reported to affect expression of genes that might influence inflammatory processes as well as genes that are important for maintaining synaptic function.