MITOCHONDRIAL-MEMBRANE FLUIDITY AND OXIDATIVE DAMAGE TO MITOCHONDRIAL-DNA IN AGED AND AD HUMAN BRAIN

Oxidative damage on biological molecules has been proposed as a major cause of alterations observed in aging brain as well as in neurodegene rative diseases. In this study, we measured membrane fluidity in mitoc hondria extracted from three cerebral regions and cerebellum of Alzhei mer disease (AD) patients and age-matched controls by means of fluores cence polarization technique. A significant reduction of mitochondrial membrane fluidity was found in AD, except in cerebellum. In controls, a decrease of membrane fluidity was observed along with age, and it w as also related to the content of the oxidized nucleoside 8-hydroxy-2' -deoxyguanosine (OH(8)dG) in mitochondrial DNA (mtDNA). Alteration in membrane fluidity seems to be a result of lipid peroxidation, since it dramatically decreased when mitochondria were exposed to FeCl2 and H2 O2. The parallel increase of viscosity in mitochondrial membrane and t he amount of OH(8)dG in mtDNA is suggestive of a relationship between these biological markers of oxidative stress. These results provide fu rther evidence that oxidative stress may play a role in the pathogenes is of AD.