Imaging of the serotonin system: Radiotracers and applications in memory disorders

Abstract

The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of serotonin (5-HT) receptors. This chapter provides the current status of radioligands used for positron emission tomography (PET) and single-photon emission computerised tomography (SPECT) imaging of the human brain 5-HT receptors and the 5-HT transporter (SERT) with particular emphasis on the applications in Alzheimer's disease (AD). Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include radiolabelled compounds for the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT4 and to some extent 5-HT6 receptors and for SERT. Imaging of serotonergic targets in humans has given invaluable insight into the normal brain function and into brain disorders where the serotonergic system is perturbed. Imaging studies show that the 5-HT1A receptor binding is increased, and 5-HT2A receptor binding is decreased in mild cognitive impairment (MCI). In early AD, 5-HT4 receptor binding is increased, whereas in early and more advanced AD, SERT and the 5-HT1A and 5-HT2A receptor binding are reduced in a region-specific manner. Future studies should focus on the association between serotonergic dysfunction and symptomatology in order to increase our understanding of the neurobiological background for neuropsychiatric symptoms in neurodegenerative and neuropsychiatric disorders.