Regional vesicular acetylcholine transporter distribution in human brain: A [18F]fluoroethoxybenzovesamicol positron emission tomography study

• Published in: Journal of comparative neurology (1911) Vol. 526; no. 17; pp. 2884 - 2897
• Main Authors: Albin, Roger L., Bohnen, Nicolaas I., Muller, Martijn L. T. M., Dauer, William T., Sarter, Martin, Frey, Kirk A., Koeppe, Robert A.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-12-2018; Wiley Subscription Services, Inc
• Subjects: Acetylcholine; Aging; Amygdala; basal forebrain; Binding sites; Brain; Brain stem; Cerebellum; Cortex (cingulate); Cortex (somatosensory); Hippocampus; Neostriatum; pedunculopontine nucleus; Positron emission tomography; RRID: SCR_001847; RRID: SCR_007037; striatum; Thalamus; Tomography; Vesicular acetylcholine transporter; striatum; basal forebrain; RRID: SCR_001847; RRID: SCR_007037; pedunculopontine nucleus; acetylcholine; aging; cerebellum; thalamus
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24541

Prior efforts to image cholinergic projections in human brain in vivo had significant technical limitations. We used the vesicular acetylcholine transporter (VAChT) ligand [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) and positron emission tomography to determine the regional distribution of VAChT binding sites in normal human brain. We studied 29 subjects (mean age 47 [range 20–81] years; 18 men; 11 women). [18F]FEOBV binding was highest in striatum, intermediate in the amygdala, hippocampal formation, thalamus, rostral brainstem, some cerebellar regions, and lower in other regions. Neocortical [18F]FEOBV binding was inhomogeneous with relatively high binding in insula, BA24, BA25, BA27, BA28, BA34, BA35, pericentral cortex, and lowest in BA17–19. Thalamic [18F]FEOBV binding was inhomogeneous with greatest binding in the lateral geniculate nuclei and relatively high binding in medial and posterior thalamus. Cerebellar cortical [18F]FEOBV binding was high in vermis and flocculus, and lower in the lateral cortices. Brainstem [18F]FEOBV binding was most prominent at the mesopontine junction, likely associated with the pedunculopontine–laterodorsal tegmental complex. Significant [18F]FEOBV binding was present throughout the brainstem. Some regions, including the striatum, primary sensorimotor cortex, and anterior cingulate cortex exhibited age‐related decreases in [18F]FEOBV binding. These results are consistent with prior studies of cholinergic projections in other species and prior postmortem human studies. There is a distinctive pattern of human neocortical VChAT expression. The patterns of thalamic and cerebellar cortical cholinergic terminal distribution are likely unique to humans. Normal aging is associated with regionally specific reductions in [18F]FEOBV binding in some cortical regions and the striatum.
Using [18F]FEOBV PET, we describe the distribution of cholinergic terminals in human brain. The distribution of cholinergic terminals is similar to that found in other mammals with some distinctive features in cortex, thalamus, and cerebellum. There are regionally specific age‐related changes in cholinergic terminal density.