Imaging of the 5-HT2A system: age-, gender-, and Alzheimer’s disease-related findings

Serotonin (5-HT) and more specifically the 5-HT2A receptor is involved in cognitive and non-cognitive behavior and plays an important role in Alzheimer’s disease (AD). The objective was to assess the 5-HT2A binding potential (BP) in healthy volunteers and AD with SPECT and 123I-5-I-R91150, a selective radio-iodinated 5-HT2A receptor antagonist. Twenty-six controls and nine AD patients were included. A semiquantitive analysis with normalization on cerebellar uptake provided estimates of BP for 26 cortical regions of interest. An age-related decline of neocortical BP was found (11.6% per decade). Compared to age-matched controls, a generally decreased neocortical BP in AD was found with a significant regional reduction in the orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. These results are in line with previous postmortem, in vitro, and PET findings. The age-related decline highlights the necessity for matched advanced age study samples. The fact that the 5-HT2A receptor is differentially affected in AD patients has implications for both the etiological basis and therapeutic management of AD.