Microscopic Evaluation of Oxidative Damage in Alzheimer Disease

Abstract In the past five years, a case for oxidative stress in the pathogenesis of Alzheimer disease (AD) has been convincingly made. That link owes most of its existence to the microscopic detection of neuronal oxidative damage. Focusing on damage not only has the advantage that stable products are studied, rather than short-lived radicals, but also that damage can be morphologically defined. This latter aspect is critical since biochemical analysis of whole tissue is mostly of the accumulated damage from normal metabolism with aging of long-lived polymers in the extracellular matrix (Figure 1). The importance of damage is that it is the result most likely to be linked to pathology. Driven by the hypothesis that oxidative damage plays a role in the aggregation of insoluble protein in the lesions of Alzheimer disease, neurofibrillary tangles and senile plaques, we developed reagents to detect protein modifications related to glycoxidation, lipid peroxidation, peroxynitrite, free carbonyls and carbonyl-modification (Figure 2).