The hormonal influence on cerebral glucose/energy metabolism.

The cerebral glucose metabolism is of pivotal significance for the maintenance of normal neuronal function and structure. There is increasing evidence that this metabolic pathway is antagonistically controlled by insulin and cortisol. During normal aging of the brain, a metalabile balance different from adult life time is formed between insulin and cortisol with functional predominance of the latter. This increases the vulnerability of the aging brain by slight damaging events. In late-onset sporadic DAT (SDAT), the function of insulin decreases further, whereas the influence of cortisol increases. As a result of this imbalance, brain glucose utilization decreases drastically producing a fall in both acetylcholine and energy synthesis. These two abnormalities participate in the formation of amyloid, and the energy deficit in the abnormal hyper-phosphorylation of tau protein. It is concluded that a disturbance in the hormonal control of the cerebral glucose/energy metabolism precedes the formation of amyloid and abnormal fibrils.