Gender and age-dependent differences in the mitochondrial apoptogenic pathway in Alzheimer's disease

Age-related mitochondrial oxidative stress is highly gender dependent. The aim of this study was to determine the role of gender in the mitochondrial contribution to neuronal apoptosis in Alzheimer's disease (AD). We used mitochondria isolated from brains of Wistar rats to study the toxicity of ss-amyloid peptide (A ss), and found that it increases mitochondrial peroxide production, nitration and oxidation of proteins, and release of cytochrome c. The toxic effects occurred in young males and in old females but not in young females, indicating their resistance to A ss. This resistance was abolished with age. These toxic effects of A ss were prevented by heme. Our findings provide a molecular mechanism for the contribution of A beta to the mitochondrial dysfunction and oxidative stress seen in AD, as well as for the mitochondria-dependent pathway of apoptosis in AD. Gender and age-related differences seen in the development of AD can also be partially explained. (C) 2008 Elsevier Inc. All rights reserved.