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

Overproduction of the peptide amyloid beta (A beta) is thought to be a crit ical pathogenetic event in Alzheimer's disease (AD). Decreasing A beta prod uction may therefore slow or halt the progression of AD. In vitro work has indicated that cholinergic muscarinic receptor agonists may reduce cellular production of A beta. Here we show that systemic administration of physost igmine, an acetylcholinesterase inhibitor, lowers A beta levels in vivo. Gu inea pigs treated for 10 days with s.c. physostigmine had levels of cortica l A betaN-40 and N-42 which were 57% and 72%, respectively, of those in con trol animals. Levels of cortical beta -amyloid precursor protein were not s ignificantly affected by drug treatment. These results suggest that choline rgic therapy may affect the course of AD by limiting A beta accumulation. ( C) 2001 Elsevier Science Ireland Ltd. All rights reserved.