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

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.

• Authors: E Perry, C Martin-Ruiz, M Lee, M Griffiths, M Johnson, M Piggott, V Haroutunian, J D Buxbaum, J Nãsland, K Davis, C Gotti, F Clementi, S Tzartos, O Cohen, H Soreq, E Jaros, R Perry, C Ballard, I McKeith, J Court
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 393 Issue 1-3 Pg. 215-22 (Mar 30 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10771016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chrna7 protein, human
• Chrna7 protein, mouse
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• nicotinic receptor alpha3beta4
• Nicotine
• Acetylcholinesterase

Topics

• Acetylcholinesterase (genetics, metabolism)
• Aging (metabolism, physiology)
• Alzheimer Disease (metabolism)
• Analysis of Variance
• Animals
• Brain (metabolism, physiology)
• Humans
• Lewy Body Disease (metabolism)
• Mice
• Mice, Transgenic
• Nicotine (metabolism)
• Receptors, Nicotinic (genetics, metabolism)
• Smoking (metabolism)
• alpha7 Nicotinic Acetylcholine Receptor