title: Elevated levels of Abeta1-40 and Abeta1-42 do not alter the binding sites of nicotinic receptor subtypes in the brain of APPswe and PS1 double transgenic mice.
abstract: The binding sites of nicotinic acetylcholine receptor (nAChR) subtypes were measured in the parietal cortex and hippocampus of transgenic mice carrying mutant human APPswe and presenilin 1 (PS1) genes (APPswe/PS1 mice) between the ages of 3 weeks and 17 months. Soluble and insoluble beta-amyloid peptide (Abeta1-40 and Abeta1-42) levels were investigated in parallel. No significant differences in binding sites of [(3)H]cytisine (alpha4beta2 nAChRs) and [(125)I]alpha-bungarotoxin (alpha7 nAChRs) were observed in APPswe/PS1 mice and wild-type control mice at any age studied. At three weeks of age, soluble Abeta1-40 was detectable in the parietal cortex and hippocampus of APPswe/PS1 mice, whereas Abeta1-42 was detectable from 12 months of age. A pronounced increase in insoluble Abeta1-42 was observed between 3 weeks and 17 months compared with that of insoluble Abeta1-40 in both brain regions, indicating a shift that favors accumulation of Abeta1-42 in older APPswe/PS1 mice. The findings indicate that elevated Abeta levels in the brains of APPswe/PS1 mice do not alter the number of alpha4beta2 and alpha7 receptors, the two major brain nAChR subtypes.
authors.affiliation: Division of Molecular Neuropharmacology, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Karolinska Institutet, Huddinge University Hospital, B84, 141 86, Stockholm, Sweden.
authors.forename: Amelia
authors.initials: A
authors.lastname: Marutle
authors.forename: Christina
authors.initials: C
authors.lastname: Unger
authors.forename: Ewa
authors.initials: E
authors.lastname: Hellström-Lindahl
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jukka
authors.initials: J
authors.lastname: Puoliväli
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation / Q000502:physiology; D010296:Parietal Lobe / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D053764:Presenilin-1; D020033:Protein Isoforms / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012016:Reference Values
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)