Molecular and Cellular Aspects of Oxidative Damage in Alzheimer's Disease

Evidence for free radical damage in Alzheimer’s disease includes damage to lipids, proteins, and nucleic acids and is likely a consequence of redox-active metal accumulations, mitochondrial damage, and the formation of advanced glycation end-products. Furthermore, free radical-mediated events are linked to all of the genetic modulators of the disease since (3-protein precursor, amyloid-p, presenilins, and apolipoprotein E are associated with reactive oxygen species production or processes intimately associated with oxidative stress such as apoptosis. An involvement of free radicals accounts for the two most striking features of Alzheimer’s disease, namely, the multitude of abnormalities affecting essentially every system and the strict age dependence. Furthermore, in therapeu­ tics, the commonality between a number of efficacious agents appears to be oxi­ dative stress reduction. In this chapter, we present evidence 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 inci­ dence or progression of Alzheimer’s disease.