Reduction of cortical amyloid β levels in guinea pig brain after systemic administration of physostigmine

Abstract

Overproduction of the peptide amyloid β (Aβ) is thought to be a critical pathogenetic event in Alzheimer's disease (AD). Decreasing Aβ production may therefore slow or halt the progression of AD. In vitro work has indicated that cholinergic muscarinic receptor agonists may reduce cellular production of Aβ. Here we show that systemic administration of physostigmine, an acetylcholinesterase inhibitor, lowers Aβ levels in vivo. Guinea pigs treated for 10 days with s.c. physostigmine had levels of cortical AβN-40 and N-42 which were 57% and 72%, respectively, of those in control animals. Levels of cortical β-amyloid precursor protein were not significantly affected by drug treatment. These results suggest that cholinergic therapy may affect the course of AD by limiting Aβ accumulation.