Alzheimer Disease: Oxidative Stress and Compensatory Responses

Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles, and senile plaques. All classes of macromolecules are affected by oxidative stress leading, inevitably, to neuronal dysfunction. Extensive data from the literature support the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, it has been suggested that in the first stage of the development of Alzheimer disease, amyloid-β deposition and hyperphosphorylated tau function as compensatory responses to ensure that neuronal cells do not succumb to oxidative damage. However, during the progression of the disease, the antioxidant activity of both agents evolves into prooxidant activity, resulting in the exacerbation of reactive oxygen species production.