Expression of Somatostatin,Cortistatin,and Their Receptors,as well as Dopamine Receptors,but not of Neprilysin,are Reduced in the Temporal Lobe of Alzheimer's Disease Patients

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive deficit, wherein the impairment of episodic memory is the major hallmark. AD patients exhibit augmented accumulation of amyloid-β (Aβ) and hyperphosphorylated tau protein in specific brain regions. In addition, several neuropeptides/neurotransmitter axes clearly associated with cognitive processes, Aβ turnover, and tau phosphorylation have also been found to be impaired in AD, such as somatostatin (SST)/cortistatin (CST) and dopamine (DA) systems. However, to date there is no precise quantitative data on the expression of these systems in the human brain of AD and normal patients. Here we measured by quantitative real-time PCR the mRNA levels of SST/CST, their receptors (sst1-5 and DA receptors (drd1-5) in addition to neprilysin (a SST-regulated enzyme involved in Aβ degradation) in three regions of the temporal lobe, one of the cortical regions most severely affected by AD. Our results reveal that some components of SST/CST- and DA-axes are divergently altered in the three areas of AD patients. Despite this region-specific regulation, an overall, common reduction of these systems was observed in the temporal lobe of AD patients. Conversely, neprilysin expression was not altered in AD, suggesting that Aβ accumulation observed in AD is due to a lack of neprilysin activation by SST rather than to a reduction of its expression. Collectively, our results define a comprehensive scenario wherein reduction of ssts, drds, and sst ligands SST and CST, could be involved, at least in part, in some of the more important defects observed in AD.