Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients

Fibroblasts from Alzheimer's disease (AD) patients displayed decreased cytochrome c oxidase (complex IV) activity (P < 0.05). The basal oxygen consumption rate (QO(2)) and the response to an uncoupler of oxidative phosphorylation did not differ between AD and control fibroblasts. The QO(2) of AD fibroblasts was more susceptible (P ( 0.05) to inhibition by azide in the range 0.5-5 mM. The basal intracellular pH (pH(i)) in AD fibroblasts was significantly more acidic than in control ones. The results support the hypothesis that subtle dysfunctions of oxidative energy-producing processes are present in fibroblasts from sporadic AD patients. The alterations observed scantly influence the fibroblasts functioning even in stressful conditions; however in tissues, such as the brain, that rely heavily on oxidative metabolism for their function, similar alterations may trigger molecular mechanisms leading to cell damage. (C) 1997 Elsevier Science Ireland Ltd.