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

Elaine Perry, Carmen Martin-Ruiz, Mandy Lee, Martin Griffiths, Mary Johnson, Margaret Piggott, Vahram Haroutunian, Joseph Daniel Buxbaum, Janne Nãsland, Kenneth Davis, Cecilia Gotti, Francesco Clementi, Socrates Tzartos, Onsat Cohen, Hermona Soreq, Evelyn Jaros, Robert Perry, Clive Ballard, Ian McKeith, Jennifer Court

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


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 α4 (but not α3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not α-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Aβ1-42, but not related to plaque or tangle densities. In contrast, α-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 α4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased α4 immunoreactivity in the cortex and lower densities of amyloid-β plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the α4 subunit in β-amyloidosis but not in nigro-striatal dopaminergic degeneration. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)215-222
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - 30 Mar 2000


  • Acetylcholinesterase
  • Alzheimer's disease
  • Parkinson's disease
  • Tobacco exposure
  • α3 subunit
  • α4 subunit
  • α7 subunit
  • β-Amyloidosis


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