Brain regional analysis of NADH-cytochrome C reductase activity in Alzheimer's disease

The specific activity of antimycin A-insensitive nicotinamide adenine dinucleotide (NADH)-dependent cytochrome C reductase, an enzyme associated with endoplasmic reticulum, was determined in the superior temporal, entorhinal, and cerebellar cortex of 16 patients who died with Alzheimer's disease and eight nondemented controls. The specific activity of choline acetyltransferase was also measured to provide an index of presynaptic cholinergic dysfunction. Our results revealed reciprocal changes in these activities that were of similar magnitude across the three regions examined. Furthermore, cytochrome C reductase activity was positively correlated with the density of neurofibrillary tangles, especially in the superior temporal cortex. These results support the hypothesis that Alzheimer's disease may be associated with an alteration of endoplasmic reticulum and the functions related to this intracellular membrane system, including the post-translational modification and localization of essential proteins.