Reactive Oxygen Species Mediate Cellular Damage in Alzheimer Disease.
The two most striking features of Alzheimer disease are (i) the multitude of abnormalities affecting essentially every system and (ii) 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 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 disease and that a reduction of oxidative stress will have a dramatic effect on reducing the incidence or progression of Alzheimer disease.
Perry
George
G
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
Castellani
Rudy J.
RJ
Hirai
Keisuke
K
Smith
Mark A.
MA