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Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases

Lookup NU author(s): Emeritus Professor Elaine Perry, Dr Carmen Martin-Ruiz, Dr Margaret Piggott, Dr Evelyn Jaros, Emeritus Professor Robert Perry, Dr Clive Ballard, Professor Ian McKeith, Dr Jennifer Court

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Abstract

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzheimer's disease or Parkinson's disease are more selective. In Alzheimer's disease, in the cortex there is a selective loss of the alpha4 (but not alpha3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not alpha-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, but not related to plaque or tangle densities. In contrast, alpha-bungarotoxin binding is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated. In Parkinson's disease, loss of striatal nicotine binding appears to occur early but is not associated with a loss of alpha4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha4 immunoreactivity in the cortex and lower densities of amyloid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the alpha4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration.


Publication metadata

Author(s): Perry E, Martin-Ruiz C, Lee M, Griffiths M, Johnson M, Piggott M, Haroutunian V, Buxbaum JD, Nasland J, Davis K, Gotti C, Clementi F, Tzartos S, Cohen O, Soreq H, Jaros E, Perry R, Ballard C, McKeith I, Court J

Publication type: Article

Publication status: Published

Journal: European Journal of Pharmacology

Year: 2000

Volume: 393

Issue: 1-3

Pages: 215-222

Print publication date: 01/01/2000

ISSN (print): 0014-2999

ISSN (electronic): 1879-0712

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/S0014-2999(00)00064-9

DOI: 10.1016/S0014-2999(00)00064-9


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