Alterations of cholinergic and serotonergic neurochemistry in alzheimer's disease: Correlations with cognitive and behavioral symptoms

Abstract

Three of the most severely affected neurotransmitter systems in AD, namely, the cholinergic, glutamatergic and serotonergic systems were investigated. M1 receptors, NMDA receptors, and 5-HT transporters were measured in the postmortem frontal and temporal cortices of two cohorts of well-characterized AD patients as well as controls. Neurochemical findings were then correlated with the rate of cognitive decline as well as behavioral changes to test the hypothesis that neurochemical alternations may underlie both cognitive decline and behavioral changes in AD. Moreover, the status of M1/G-protein coupling in AD was measured and correlated with cognitive decline as well as with measurements of ChAT, PKC and Src kinase activities to investigate the possible interactions between M1 receptor mediated signaling and NMDA receptor status. Besides, the effects of two functional gene polymorphisms (i.e. APOE i?Y4 allele and LL genotype of the promoter region of 5-HTT) on the cholinergic and serotonergic systems, respectively, were examined.