Selective Nicotinic Receptor Consequences in APPSWE Transgenic Mice

The nicotinic (nAChRs) and muscarinic (mAChRs) acetylcholine receptors and acetylcholinesterase (AChE) activity were studied in the brains of APPSWE transgenic mice (Tg+) and age-matched nontransgenic controls (Tg−) that were between 4 and 19 months of age. A significant increase in the binding of 125I-labeled α-bungarotoxin (α7 nAChRs) was observed in most brain regions analyzed in 4-month-old Tg+ mice, preceding learning and memory impairments and amyloid-β (Aβ) pathology. The enhanced α7 receptor binding was still detectable at 17–19 months of age. Increase in [3H]cytisine binding (α4β2 nAChRs) was measured at 17–19 months of age in Tg+ mice, at the same age when the animals showed heavy Aβ pathology. No significant changes in [3H]pirenzepine (M1 mAChRs) or [3H]AFDX 384 (M2 mAChRs) binding sites were found at any age studied. The upregulation of the nAChRs probably reflects compensatory mechanisms in response to Aβ burden in the brains of Tg+ mice.