Alzheimer disease (AD) leads to alterations in several biochemical properties in cultured skin fibroblasts. Because abnormal glucose metabolism has been reported in both in vivo and in vitro studies of the brain, we examined glucose and glutamine oxidation and lactate production in cultured skin fibroblasts from nine patients with familial AD, 19 with sporadic AD, and 20 age-matched controls. The production of CO2from glucose and glutamine was significantly lower in both groups of Alzheimer fibroblasts compared to controls after 10 min or 1, 2, and 4 h of incubation. The reduction in CO2production was most evident after 1 h of incubation with either (U-4C)-glucose or (U-4C)-glutamine. Lactate concentration was comparable in all groups at any time of incubation. These findings suggest that processes that require mitochondrial function as glucose or glutamine oxidation are altered in AD and provide evidence that complex metabolic differences are expressed in cultured nonneuronal cells from Alzheimer patients.