What protects patients with schizophrenia from developing alzheimer pathology?

Abstract

Disturbed insulin signal transduction and increased glycogen synthase kinase-3beta expression/activity are core features of Alzheimer's disease (AD). Moreover, compromised insulin signalling (including reduced insulin-degrading enzyme activity) is blamed to significantly contribute to the development of typical hallmarks of AD: amyloid deposits and hyperphosphorylation of tau protein. Interestingly, patients with schizophrenia often suffer from the metabolic syndrome. Treatment with typical and atypical neuroleptics either initiates or further increases the metabolic problems of many schizophrenics. In post-mortem brains of schizophrenics considerable functional decrease of insulin receptors, disruption of the Akt-dependent insulin signalling system, and increased glycogen synthase kinase-3beta expression/activity have been found. The striking similarities of pathologic changes in brain insulin metabolism of schizophrenics and AD patients should lead to an increased incidence of AD in aged schizophrenics. Remarkably, this is not the case. We try to identify possible protective mechanisms that prevent AD pathology in patients with schizophrenia.