Genetics, lifestyle and the roles of amyloid beta and oxidative stress in Alzheimer's disease.
This paper reviews a wide range of recent studies that have linked AD-associated biochemical and physiological changes with oxidative stress and damage. Some of these changes include disruptions in metal ion homeostasis, mitochondrial damage, reduced glucose metabolism, decreased intracellular pH and inflammation. Although the changes mentioned above are associated with oxidative stress, in most cases, a cause and effect relationship is not clearcut, as many changes are interlinked. Increases in the levels of Abeta peptides, the main protein components of the cerebral amyloid deposits of AD, have been demonstrated to occur in inherited early-onset forms of AD, and as a result of certain environmental and genetic risk factors. Abeta peptides have been shown to exhibit superoxide dismutase activity, producing hydrogen peroxide which may be responsible for the neurotoxicity exhibited by this peptide in vitro. This review also discusses the biochemical aspects of oxidative stress, antioxidant defence mechanisms, and possible antioxidant therapeutic measures which may be effective in counteracting increased levels of oxidative stress. In conclusion, this review provides support for the theory that damage caused by free radicals and oxidative stress is a primary cause of the neurodegeneration seen in AD with Abeta postulated as an initiator of this process.
Veurink
G
G
The Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Australia.
Fuller
S J
SJ
Atwood
C S
CS
Martins
R N
RN
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology; D001057:Apolipoproteins E / Q000502:physiology; D004032:Diet; D005609:Free Radicals / Q000009:adverse effects; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D005609:Free Radicals; D017382:Reactive Oxygen Species