Oxidative Stress and Alzheimer’s Disease

Oxidative stress is the inevitable result of life’s requirement to reduce molecular oxygen to water for cellular respiration and energy metabolism. For a number of reasons, the human brain appears particularly vulnerable to oxidative stress, which has necessitated elaboration of complex antioxidant defenses in order to maintain oxidative balance. With advanced age, oxidative balance wanes in favor of oxidative stress, which sometimes results in disease, in particularly age associated sporadic or environmentally driven diseases such as Alzheimer’s disease, cardiovascular disease, and cancer. Over the last 20 years, our laboratory has investigated oxidative stress by numerous in situ techniques and have identified oxidative stress-associated adducts, redox active transition metals, and metal associated proteins, not only within pathological lesions of the AD brain, but also unaffected brain prior to the onset of overt structural pathology. We have further demonstrated that oxidative stress decreases with increasing pathology, especially amyloid, suggesting that hallmark lesions in AD are more likely a productive response than a deleterious event. These and other findings continue to indicate the need to examine oxidative stress in greater detail, as well as expand the universe of antioxidant therapies, particularly as classical lesion-based therapies continue to fail.