Insulin, Insulin Receptors, and Igf-I Receptors in Post-Mortem Human Brain in Alzheimer’s Disease

In dementia of Alzheimer type (SDAT), reductions in glucose metabolism in vivo (Kumar et al., 1991). reduced activities of enzymes involved in glycolytic and oxidative glucose breakdown were reported in post-mortem brain tissue (Perry et al., 1980, Gibson et al., 1988). These reductions appeared to be more severe than the “nonspecific’.reductions in a number of biochemical constituents that had been related to brain atrophy (Bowen et al., 1979). Thus, the hypothesis has been forwarded that defects in the regulation of glucose metabolism, i.e. due to changes in CNS insulin receptor function, might be an early contributing event to the onset of SDAT (Hoyer, 1996). Brain insulin regulates enzymes of cerebral glucose metabolism via specific high-affinity insulin receptors, which differ from peripheral insulin receptors in the amount of glycosylation (Baskin et al., 1988, Wozniak et al., 1993, dePablo & de la Rosa, 1995). Furthermore, insulin also binds to insulin-like growth factor I receptors and via these receptors possibly exerts trophic effects on neuronal cells and interacts with cholinergic neurotransmission (Calissano et al., 1993, Quirion et al., 1991, Rotwein, 1991, Kyriakis et al., 1987).