title: 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.affiliation: Department of Neuropathology, MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Road, Newcastle, UK. e.k.perry@ncl.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Perry
authors.forename: C
authors.initials: C
authors.lastname: Martin-Ruiz
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Griffiths
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Piggott
authors.forename: V
authors.initials: V
authors.lastname: Haroutunian
authors.forename: J D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: J
authors.initials: J
authors.lastname: Nãsland
authors.forename: K
authors.initials: K
authors.lastname: Davis
authors.forename: C
authors.initials: C
authors.lastname: Gotti
authors.forename: F
authors.initials: F
authors.lastname: Clementi
authors.forename: S
authors.initials: S
authors.lastname: Tzartos
authors.forename: O
authors.initials: O
authors.lastname: Cohen
authors.forename: H
authors.initials: H
authors.lastname: Soreq
authors.forename: E
authors.initials: E
authors.lastname: Jaros
authors.forename: R
authors.initials: R
authors.lastname: Perry
authors.forename: C
authors.initials: C
authors.lastname: Ballard
authors.forename: I
authors.initials: I
authors.lastname: McKeith
authors.forename: J
authors.initials: J
authors.lastname: Court
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009538:Nicotine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403530:nicotinic receptor alpha3beta4; D009538:Nicotine; D000110:Acetylcholinesterase