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Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer, Parkinson and Lewy body types

Lookup NU author(s): Emeritus Professor Elaine Perry, Dr Jennifer Court, Emeritus Professor Robert Perry

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Abstract

Cholinergic nicotinic and muscarinic receptor binding were measured in post mortem human brain tissue, using low (nM) concentrations of (3H)-nicotine to detect predominately the high affinity nicotinic site and (3H)-N-methylscopolamine in the presence and absence of 3×10−4 M carbachol to measure both the low and high affinity agonist subtypes of the muscarinic receptor group. Consistent with most previous reports, the nicotinic but not muscarinic binding was reduced in the different forms of dementia associated with cortical cholinergic deficits, including Alzheimer's and Parkinson's disease, senile dementia of Lewy body type (SDLT) and Down's syndrome (over 50 years). Analysis of (3H)-nicotine binding displaced by a range of carbachol concentrations (10−9–10−3 M) indicated 2 binding sites for nicotine and that the high affinity rather than low affinity site was reduced in Alzheimer's disease. In all 3 cortical areas investigated (temporal, parietal and occipital) there were increases in the low affinity muscarinic site in Parkinson's disease and SDLT but not Alzheimer's disease or middle-aged Down's syndrome. This observation raised the question of whether the presence of neurofibrilalry tangles (evident in the latter but not former 2 disorders) is incompatible with denervation-induced muscarinic supersensitivity in cholinoceptive neurons which include cortical pyramids generally affeced by tangle formation.


Publication metadata

Author(s): Perry EK, Smith CJ, Court JA, Perry RH

Publication type: Article

Publication status: Published

Journal: Journal of Neural Transmission – Parkinson’s Disease and Dementia Section

Year: 1990

Volume: 2

Issue: 3

Pages: 149-158

Print publication date: 01/01/1990

ISSN (print):

ISSN (electronic): 1435-1463

Publisher: Springer

URL: http://dx.doi.org/10.1007%2FBF02257646

DOI: 10.1007%2FBF02257646


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