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Intact coupling of M1 receptors and preserved M2 and M4 receptors in the cortex in progressive supranuclear palsy: Contrast with other dementias

Lookup NU author(s): Dr Naomi Warren, Dr Margaret Piggott, Emeritus Professor Elaine Perry, Professor David Burn


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Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterised clinically by motor and cognitive symptoms. Cholinergic dysfunction is thought to be responsible for much of the cognitive symptomatology. To date, however, cholinergic replacement therapies have been ineffective. We used receptor specific radioligand autoradiography to measure M1, M2, and M4 receptor density, and the functional status of the principal cortical subtype, M1, in the frontal cortex in post-mortem brain tissue of PSP patients (n = 14). Results were compared to normal controls (n = 17) and patients with dementia with Lewy bodies (DLB, n = 12) and Alzheimer's disease (AD, n = 15). In PSP there were no changes in M1, M2, or M4 muscarinic receptor densities or M1 coupling. DLB cases showed a non-significant increase in M1 receptors. In AD there was a reduction in M1 receptors and coupling in most frontal cortical areas which reached significance, compared to DLB, for M1 receptors in the cingulate (p < 0.05). We conclude from this first systematic study of cortical muscarinic receptors in PSP that functioning cortical muscarinic receptors are preserved. A further, larger trial of cholinergic therapy, such as an M1 agonist, may be warranted. © 2008 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Warren NM, Piggott MA, Lees AJ, Perry EK, Burn DJ

Publication type: Article

Publication status: Published

Journal: Journal of Chemical Neuroanatomy

Year: 2008

Volume: 35

Issue: 3

Pages: 268-274

ISSN (print): 0891-0618

ISSN (electronic): 1873-6300

Publisher: Elsevier BV


DOI: 10.1016/j.jchemneu.2008.01.001

PubMed id: 18282687


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Funder referenceFunder name
G0400074Medical Research Council
G0502157Medical Research Council