title: Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies by immunoprecipitation.
abstract: Antibodies raised against human alpha2-6 and beta2-4 nicotinic receptor subunits were utilized to fractionate (3)H-epibatidine binding in human temporal cortex and striatum. The predominant receptor subtypes in both regions contained alpha4 and beta2 subunits. In normal cortex, 10% of binding was also associated with alpha2 subunits, whereas in the striatum, contributions by alpha6 (17%) and beta3 (23%) were observed. Minimal binding (< or =5%) was associated with alpha3. In Alzheimer's disease and dementia with Lewy bodies, cortical loss of binding was associated with reductions in alpha4 (50%, P < 0.01) and beta2 (30-38%, P < 0.05). In Parkinson's disease and dementia with Lewy bodies, striatal deficits in alpha6 (91 and 59% respectively, P < 0.01) and beta3 (72 and 75%, P < 0.05) tended to be greater than for alpha4 and beta2 (50-58%, P < 0.05). This study demonstrates distinct combinations of subunits contributing to heteromeric nicotinic receptor binding in the human brain that are area/pathway specific and differentially affected by neurodegeneration.
authors.affiliation: CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gotti
authors.forename: Milena
authors.initials: M
authors.lastname: Moretti
authors.forename: Iwo
authors.initials: I
authors.lastname: Bohr
authors.forename: Iryna
authors.initials: I
authors.lastname: Ziabreva
authors.forename: Silvia
authors.initials: S
authors.lastname: Vailati
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.forename: Loredana
authors.initials: L
authors.lastname: Riganti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Gaimarri
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
authors.forename: Robert H
authors.initials: RH
authors.lastname: Perry
authors.forename: Dag
authors.initials: D
authors.lastname: Aarsland
authors.forename: Jan Petter
authors.initials: JP
authors.lastname: Larsen
authors.forename: Emanuele
authors.initials: E
authors.lastname: Sher
authors.forename: Ruth
authors.initials: R
authors.lastname: Beattie
authors.forename: Francesco
authors.initials: F
authors.lastname: Clementi
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Court
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D000595:Amino Acid Sequence; D001344:Autopsy; D003342:Corpus Striatum / Q000473:pathology*; D005260:Female; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics; D013702:Temporal Lobe / Q000473:pathology*
chemical_list: D010446:Peptide Fragments; D011978:Receptors, Nicotinic