Altered metabolic properties of cultured skin fibroblasts in Alzheimer's disease

Abstract

Alzheimer's disease is associated with selective neuronal loss, the cause of which is undetermined. Evidence indicating a predisposing genetic factor associated with this disease suggests that important alterations may be expressed in tissues other than the brain. Because abnormal glucose and energy-related metabolism have been identified in both in vivo and in vitro studies of brain, we conducted a study to examine related measures in cultured skin fibroblasts from six patients with Alzheimer's disease and seven age-matched controls. After 60 minutes' incubation, the production of ¹⁴CO₂ from [U-¹⁴C]glucose and lactate production were significantly higher in the cells from the group of patients with Alzheimer's disease. The increase of ¹⁴CO₂ production, but not the production of lactate, was most evident after a more rapid period of metabolic activity in the first 10 minutes of incubation. By contrast, ¹⁴CO₂ production from [U-¹⁴C]glutamine, which is probably the major substrate of oxidative metabolism in these cells, was significantly reduced in the Alzheimer's disease cells following longer (120-minute) incubations. Oxygen uptake by cell suspensions was also significantly reduced in the group with Alzheimer's disease. These results indicate that complex metabolic differences are expressed in nonneural tissues from some patients with Alzheimer's disease and may provide important clues to the pathogenesis of this disorder.