No association between Alzheimer plaques and decreased levels of cytochrome oxidase subunit mRNA, a marker of neuronal energy metabolism

It has been proposed that neuritic plaques or toxic substances diffusing from them contribute to neurodegeneration in Alzheimer disease. We examined this hypothesis by looking for evidence of decreased neuronal energy metabolism in the proximity of neuritic plaques. Levels of mitochondrial DNA-encoded mRNA for subunit III of cytochrome oxidase, a marker of neuronal energy metabolism, were determined in post mortem brain samples. Consistent with earlier results, overall cytochrome oxidase subunit III mRNA levels were decreased in Alzheimer midtemporal cortex compared with controls. However, this reduction did not correlate with plaque density. In Alzheimer brains, cytochrome oxidase subunit III mRNA levels in neurons bearing neurofibrillary tangles were lower than in tangle-free neurons. However, neuronal cell bodies in close proximity of neuritic plaques showed no decrease in cytochrome oxidase subunit III mRNA or total polyadenylated mRNA compared with more distant neurons. Cytochrome oxidase enzyme activity in neuronal processes also showed no local reduction around neuritic plaques. These results suggest that neuritic plaques do not contribute to reduced neuronal energy metabolism in Alzheimer disease.