Elevated levels of Aβ1–40 and Aβ1–42 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 β-amyloid peptide (Aβ1–40 and Aβ1–42) levels were investigated in parallel. No significant differences in binding sites of [ 3H]cytisine (α4β2 nAChRs) and [ 125I]α-bungarotoxin (α7 nAChRs) were observed in APPswe/PS1 mice and wild-type control mice at any age studied. At three weeks of age, soluble Aβ1–40 was detectable in the parietal cortex and hippocampus of APPswe/PS1 mice, whereas Aβ1–42 was detectable from 12 months of age. A pronounced increase in insoluble Aβ1–42 was observed between 3 weeks and 17 months compared with that of insoluble Aβ1–40 in both brain regions, indicating a shift that favors accumulation of Aβ1–42 in older APPswe/PS1 mice. The findings indicate that elevated Aβ levels in the brains of APPswe/PS1 mice do not alter the number of α4β2 and α7 receptors, the two major brain nAChR subtypes.