Regional distribution and behavioral correlates of 5-HT_2A receptors in Alzheimer's disease with [¹⁸F]deuteroaltanserin and PET

Abstract 

Postmortem studies show reductions in brain serotonin 2A (5-HT_2A) receptors in Alzheimer's disease (AD). Converging evidence also suggests that serotonergic dysregulation may contribute to behavioral symptoms that frequently occur in AD. This study aimed to define regional reductions in 5-HT_2A binding in AD patients and to examine their behavioral correlates. Nine patients with probable AD and eight elderly controls were studied using a constant infusion paradigm for equilibrium modeling of [¹⁸F]deuteroaltanserin with positron emission tomography (PET). Region of interest analyses were performed on PET images coregistered to MRI scans. The outcome measures BP_P (ratio of specific brain uptake to total plasma parent concentration) and BP_ND (ratio of specific to nondisplaceable uptake) were obtained for pertinent cortical and subcortical regions. AD patients showed a statistically significant decrease in the anterior cingulate in both BP_P and BP_ND, but in no other region. Within the AD patient sample, no significant correlations were observed between regional 5-HT_2A binding and behavioral measures, including depressive and psychotic symptoms. These results confirm a reduction in cortical 5-HT_2A receptors in AD, specifically in the anterior cingulate. However, in a limited AD patient sample, they fail to demonstrate a relationship between regional 5-HT_2A binding and major behavioral symptoms.

Keywords: Alzheimer's disease, [¹⁸F]deuteroaltanserin, 5-HT_2A receptor, Serotonin, Positron emission tomography, Anterior cingulate