Mitochondria from Alzheimer's fibroblasts show decreased uptake of calcium and increased sensitivity to free radicals

Abstract

Many of the biological abnormalities seen in samples of the brain and other tissues from patients with Alzheimer's disease, are consistent with an excessive action of oxygenic free radicals. Mitochondria from fibroblasts grown in tissue culture from skin samples taken at autopsy from patients with histologically confirmed Alzheimer's disease, take up significantly less calcium than do fibroblast mitochondria from age matched non-demented controls. Following exposure to oxygenic free radicals generated by adding ferrous ions to the incubation mixture, calcium uptake is increased to a greater extent in Alzheimer's mitochondria than in controls. At the doses used, pretreatment with the lazaroid antioxidant drug U-74500A, or with the iron chelator deferoxamine, prevents the free radical induced increase in calcium uptake by control mitochondria, but provides only partial protection for Alzheimer's mitochondria. These observations suggest that Alzheimer's fibroblast mitochondria have impaired calcium transport processes and show increased sensitivity to oxygenic free radicals.