Muscarinic receptor binding changes in postmortem Parkinson’s disease

Caitlin McOmish, Geoff Pavey, Catriona McLean, Malcolm Horne, Brian Dean, Elizabeth Scarr

Parkinson's disease (PD) is a devastating disorder, affecting approximately 2% of people aged 60 and above. It is marked by progressive neurodegeneration that has long been known to impact dopaminergic cells and circuits, but more recently the acetylcholine system has also been implicated in the complex aetiology and symptomatology of the disease. While broad changes in cholinergic markers have been described, insight into the contribution of specific acetylcholine receptors is less clear. To address this important unknown, in this study we performed [(3)H] pirenzepine, [(3)H] 4DAMP, and [(3)H] AF-DX 384 in situ radioligand binding on postmortem tissues from Brodmann's area 6, 9, 46, and the caudate putamen, from PD and matched controls to detect muscarinic M1, M3, and M1/2/4 receptors, respectively. We found no difference in [(3)H] pirenzepine binding between PD and controls across all regions assessed. [(3)H] 4DAMP binding was found to be higher in PD CPu and BA9 than in controls. [(3)H] AF-DX 384 was higher in BA9 of PD compared with controls. In sum, we show selective increase in M3 receptors in cortical and subcortical regions, as well as increased M2/M4 in cortical area BA9, which together support a role for cholinergic dysfunction in PD.