Effects of aging and beta-amyloid on the properties of brain synaptic and mitochondrial membranes.

The effects of aging and of different amyloid beta-peptides (A beta) on the properties of purified synaptosomal plasma and mitochondrial membranes were studied using different fluorescent dyes. Aging led to opposite membrane alterations in both mouse brain fractions. Cholesterol levels were significantly enhanced in synaptosomal plasma membranes (SPM) from aged mice only. Flexibility of membrane fatty acids was decreased in synaptosomal plasma and mitochondrial membranes, mobility of pyrene was enhanced, but in SPM only. With regard to acyl chain flexibility in aged brain membranes, both membrane preparations were less sensitive to A beta. By contrast, effects of A beta on the mobility of pyrene were not reduced for aged synaptic membranes, but even seemed to be enhanced in the case of aged mitochondrial membranes. The data presented significantly enhance our understanding of the mechanism of the A beta's disordering effects on synaptosomal membranes that are also detectable for mitochondrial membranes and show for the first time that A beta effects are modified by brain aging. This is of special interest since membrane alterations and in particular modifications of membrane cholesterol were recently linked to Alzheimer's Disease.