A Disturbance in the Neuronal Insulin Receptor Signal Transduction in Sporadic Alzheimer's Disease

: Disturbances of glucose and energy metabolism are hypothesized as pathogenetic factors in sporadic dementia of Alzheimer type (SDAT). Insulin and is receptors play an important role in the regulation of brain glucose metabolism and neuronal growth. In postmortem brain cortex in SDAT, the densities of brain insulin receptors were decreased compared to adult controls, but were increased in relation to aged controls. Tyrosine kinase activity, a signal transduction mechanism common to insulin and IGF-1 receptors, was reduced in SDAT in comparison to middle-aged and age-matched control groups. The data are consistent with a neurotrophic role of insulin in the human brain and an upregulation of insulin receptors is SDAT brain as a compensatory mechanism, possibly due to impaired signal transduction mechanism.