Statins and Reduction of Oxidative Stress in the Aged Brain

A strong relationship between metabolic syndromes such as hyperlipidemia or hyperglycemia and dementia has been suggested in many cell culture and animal studies. Both hypercholesterolemia and oxidative stress may be involved in the molecular mechanism underlying Alzheimer's disease (AD), and lipid peroxidation products such as 4-hydroxy-2-nonenal were actually elevated in the brains of AD patients. Meanwhile, hyperglycemia and insulin resistance also lead to a number of pathological processes, including oxidative stress, advanced glycation end products formation, and insulin-signaling impairment in the central nervous system. Statins, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors currently in worldwide clinical use for treatment of hyperlipidemia, reduce levels of cortical amyloid β and oxidative stress with or without affecting cholesterol levels. As statins show various pleiotropic effects, they have high potential as a therapeutic approach to AD.