Muscarinic receptors in the thalamus in progressive supranuclear palsy and other neurodegenerative disorders

Abstract

Progressive supranuclear palsy (PSP) is a neurodegenerative disease with motor, cognitive, and behavioral symptomatology. Cholinergic dysfunction is thought to underpin several key symptoms. There is known pathologic involvement of the corticobasal ganglia-thalamocortical loops in PSP, but little attention has been focused on potential thalamic dysfunction. Using autoradiography, we measured muscarinic M2 and M4 receptors in specific thalamic nuclei involved in the limbic and motor loops in patients with PSP (n = 11) and compared results from brain tissue of subjects with Lewy body dementias (including dementia with Lewy bodies and Parkinson disease with dementia, n = 31), Alzheimer disease (n = 22) and normal elderly control subjects (n = 27). In the thalamus M2 receptors were more abundant than M4 receptors and were most densely concentrated in the anteroprincipal (AP) and mediodorsal (MD) nuclei, which connect to limbic cortices. M2 receptor binding was reduced in the AP nucleus in PSP compared with control subjects and those with Lewy body dementias. M4 receptors were markedly reduced in the MD nucleus in those with PSP compared with control subjects. M4 receptors were also reduced in the subthalamic nucleus in patients with PSP. M4 receptor binding was reduced in the MD nucleus in the Lewy body dementia and Alzheimer disease groups compared with control subjects. There were no significant changes in the ventrolateral nucleus (motor). Cholinergic dysfunction within the AP and MD nuclei of the thalamus may contribute to behavioral and cognitive disturbances associated with PSP. © 2007 American Association of Neuropathologists, Inc.