OXIDATIVE-METABOLISM IN CULTURED FIBROBLASTS DERIVED FROM SPORADIC ALZHEIMERS-DISEASE (AD) PATIENTS

Fibroblasts from Alzheimer's disease (AD) patients displayed decreased cytochrome c oxidase (complex IV) activity (P < 0.05). The basal oxyg en consumption rate (QO(2)) and the response to an uncoupler of oxidat ive phosphorylation did not differ between AD and control fibroblasts. The QO(2) of AD fibroblasts was more susceptible (P ( 0.05) to inhibi tion 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 oxida tive energy-producing processes are present in fibroblasts from sporad ic AD patients. The alterations observed scantly influence the fibrobl asts functioning even in stressful conditions; however in tissues, suc h as the brain, that rely heavily on oxidative metabolism for their fu nction, similar alterations may trigger molecular mechanisms leading t o cell damage. (C) 1997 Elsevier Science Ireland Ltd.