Abnormalities of mitochondrial enzymes in Alzheimer disease.

Abundant evidence, including critical information gathered by Prof. Siegfried Hoyer and his colleagues, indicates that abnormalities of cerebral metabolism are common in neurodegenerative diseases, including Alzheimer's Disease (AD). Alterations in mitochondrial enzymes likely underlie these deficits. Replicable reductions in AD brain occur in the pyruvate dehydrogenase complex (the link of glycolysis to the Kreb's cycle), the alpha-ketoglutarate dehydrogenase complex (KGDHC; the link of Kreb's cycle to glutamate metabolism) and cytochrome oxidase (the link of the Kreb's cycle to oxygen utilization). Available evidence suggests that deficiencies in KGDHC may be genetic in some cases, whereas evidence that the other two enzyme systems have a genetic component is lacking. Additional results indicate that the reductions can also be secondary to other causes including oxidative stress. A variety of data suggest that the mitochondrial insufficiencies contribute significantly to the pathophysiology of AD.