Oxidative energy metabolism in Alzheimer brain

Abstract

Reduction of the cerebral metabolic rate of glucose is one of the most predominant abnormalities generally found in the Alzheimer brain, whereas the cerebral metabolic rate of oxygen is only slightly diminished or not at all the beginning of this dementive disorder. This metabolic abnormality may induce severe functional disturbances, obviously preceding morphobiological changes. From the cerebral metabolic rates of oxidized glucose and oxygen, the cerebral ATP formation rate was calculated in incipient early-onset, incipient late-onset and stable advanced dementia of Alzheimer type. A reduction of ATP formation was found from at least 7% in incipient early-onset, to around 20% in incipient late-onset DAT, and from 35% to more than 50% in stable advanced dementia. This approximation was adjusted to findings demonstrating diminished activities of enzymes active in glucose metabolism and formation of oxidation equivalents for ATP production from substrates other than glucose. A reduction for energy formation to the same rrange was found, as was also recently reported, in vivo in Alzheimer patients. From this rather theoretical point of view, a permanent loss of energy by at least 7–20% in incipient and progressively advancing dementia of the Alzheimer type may by assumed, with an increasing tendency in stable advanced dementia to around 50% energy loss. This energy deficit may have drastic impacts on brain function.