[Is the lesion produced by oxidation a central part in the pathogenesis of Alzheimer's disease?].
The two most striking features of Alzheimer's disease are: a) the multitude of abnormalities affecting essentially every system, and b) the strict age dependence. Recent work suggests that both features are linked to increased oxidative stress that damages lipids, proteins and nucleic acids and results in redox-active metal accumulations, mitochondrial damage and formation of advanced glycation endproducts. Interestingly, beta-protein precursor, amyloid-beta, presenilins and apolipoprotein E have all been linked to reactive oxygen species production or with apoptosis, a process intimately associated with oxidative stress. In therapeutics, the commonality between a number of efficacious agents appears to be oxidative stress reduction. Therefore, we contend that oxidative stress is the element that links the multitude of changes in Alzheimer's disease and that a reduction of oxidative stress will have a dramatic effect on reducing the incidence or progression of Alzheimer's disease.
Perry
G
G
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. gxp7@po.cwru.edu
Smith
M A
MA
D000544:Alzheimer Disease / Q000175:diagnosis / Q000209:etiology*; D005609:Free Radicals / Q000009:adverse effects; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000502:physiology
D005609:Free Radicals; D017382:Reactive Oxygen Species