Regional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer's disease with [18F]deuteroaltanserin and PET

Postmortem studies show reductions in brain serotonin 2A (5-HT2A) 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-HT2A 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 BPP (ratio of specific brain uptake to total plasma parent concentration) and BPND (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 BPP and BPND, but in no other region. Within the AD patient sample, no significant correlations were observed between regional 5-HT2A binding and behavioral measures, including depressive and psychotic symptoms. These results confirm a reduction in cortical 5-HT2A receptors in AD, specifically in the anterior cingulate. However, in a limited AD patient sample, they fail to demonstrate a relationship between regional 5-HT2A binding and major behavioral symptoms.