Involvement of an altered 5-HT6 receptor function in behavioral symptoms of Alzheimer's disease

Abstract

We studied the hypothesis that disturbances in 5-HT receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavioral symptoms. cAMP formation after stimulation with the selective 5-HT receptor agonist E-6801 was significantly lower (p<0.01) in AD (170.02 ± 27.53 pmol/mg prot.) compared to controls (823.33 ±196.67). In addition, the ratio cAMP formation after stimulation with E-6801/5-HT receptor density was significantly lower (p< 0.01) in AD (6.67 ± 0.83) compared to controls (16.67 ± 3.33). Splitting these results by sex, 5-HT receptor activation was significantly lower (p<0.01) in AD females compared to males (121.67 ± 30.02 vs. 231.67 ± 34.17 pmol/mg prot). 5-HT density and 5-HT levels were significantly correlated (p≤0.01) in both controls and AD patients, although in AD, this correlation was lost in females. Psychosis factor was the best predictor of reduced 5-HT levels or adenylate cyclase activity after E-6801 stimulation, the former result being due to females. It may be suggested that psychotic symptoms may be related to a dysregulation of 5-HT activation by 5-HT in the temporal cortex. These results are discussed in terms of purported influence of sex and therapeutical approaches to psychosis in AD. © 2008 - IOS Press and the authors. All rights reserved.