Oxidative processes in the brain and non-neuronal tissues as biomarkers of Alzheimer's disease

Abstract

Diminished metabolism and excessive oxidative stress occur in the brains of patients with Alzheimer's Disease (AD). These abnormalities in oxidative processes occur in the brain in early stages of AD, which suggests that the deficits are not just secondary to the neuro-degeneration. Alterations in oxidative processes also occur in early stages of AD in non-neuronal tissues including fluids (e.g., cerebrospinal fluid, plasma and urine), cell like particles (e.g., red blood cells and platelets) and cells (e.g., lymphocytes). AD-related abnormalities also persist in cultured cells such as fibroblasts, which indicates that the AD-related changes are not secondary to pathology, and reflect inherent properties of AD cells. These measures of abnormalities in oxidative processes in peripheral cells from AD patients have the potential to be useful as diagnostic markers, as indicators of the progression of the disease, as a tool to develop therapeutic approaches and as monitors of therapeutic efficacy. The peripheral cells are also useful for discovering mechanisms that underlie the multiple changes in cell signaling pathways that accompany AD. Several experimental approaches suggest that oxidative stress is a convergence factor that leads to many other AD-related changes. This review focuses on the considerable recent progress in the quest for markers of metabolism/oxidative stress in peripheral tissues from AD patients, and on experiments to test their pathophysiological importance.