Functional alterations in Alzheimer's disease: diminution of cytochrome oxidase in the hippocampal formation.

In Alzheimer's disease, the relationship between structural alterations such as neurofibrillary tangles and senile plaques and neuronal function is unknown. Cytochrome oxidase, the terminal enzyme of the electron transport, is a marker of neuronal functional activity. Its activity is diminished in experimentally deafferented neurons. Based on evidence that the molecular layer of the dentate gyrus is deafferented in the brains of individuals with Alzheimer's disease, we hypothesized that cytochrome oxidase activity would be diminished in this region secondary to reduced glutamatergic input. Using cytochrome oxidase histochemistry, we found a change in the distribution of cytochrome oxidase in the molecular layer of the dentate gyrus and a decrease in activity in both the dentate gyrus and hippocampal subfields in Alzheimer's disease. In contrast, we found relatively little structural pathology in the dentate gyrus, CA4, and CA3 in these individuals. These results suggest that neurons that remain structurally intact in Alzheimer's disease may nonetheless undergo changes in metabolic function as neural systems fail.