MITOCHONDRIA FROM ALZHEIMERS FIBROBLASTS SHOW DECREASED UPTAKE OF CALCIUM AND INCREASED SENSITIVITY TO FREE-RADICALS

Many of the biological abnormalities seen in samples of the brain and other tissues from patients with Alzheimer's disease, are consistent w ith an excessive action of oxygenic free radicals. Mitochondria from f ibroblasts 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 ra dicals generated by adding ferrous ions to the incubation mixture, cal cium uptake is increased to a greater extent in Alzheimer's mitochondr ia than in controls. At the doses used, pretreatment with the lazaroid antioxidant drug U-74500A, or with the iron chelator deferoxamine, pr events the free radical induced increase in calcium uptake by control mitochondria, but provides only partial protection for Alzheimer's mit ochondria. These observations suggest that Alzheimer's fibroblast mito chondria have impaired calcium transport processes and show increased sensitivity to oxygenic free radicals.