Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: an update.

It is discussed that Alzheimer disease does not form a nosologic entity. 5 to 10% of all Alzheimer cases are due to inherited abnormalities on chromosomes 1, or 14, or 21, whereas the majority of 90-95% is sporadic in origin. Age-related changes in the composition of membranes and in glucose/energy metabolism along with a sympathetic tone in the brain are assumed to be cellular/molecular risk factors for this disease. In its pathogenesis, the desensitization of the neuronal insulin receptor similar to non-insulin dependent diabetes mellitus may be of pivotal significance. This abnormality along with a reduction in insulin concentration is assumed to induce a cascade-like process of disturbances including decreases in cellular glucose, acetylcholine, cholesterol, and ATP, associated with changes in the metabolism of amino acids and fatty acids. There is evidence that the reductions in the availability of both glucose/energy and insulin contribute to the formation of amyloidogenic derivatives and hyperphosphorylated tau protein. This may indicate that the amyloid cascade hypothesis in not valid for sporadic Alzheimer disease but that the formation of both, amyloidogenic derivatives and hyperphosphorylated tau protein is downstream the origin of this neurodegenerative disease.