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.
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.
Marutle
Amelia
A
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.
Unger
Christina
C
Hellström-Lindahl
Ewa
E
Wang
Jun
J
Puoliväli
Jukka
J
Tanila
Heikki
H
Nordberg
Agneta
A
Zhang
Xiao
X
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
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)