Reduction of cortical amyloid beta levels in guinea pig brain after systemic administration of physostigmine.
Overproduction of the peptide amyloid beta (Abeta) is thought to be a critical pathogenetic event in Alzheimer's disease (AD). Decreasing A 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 Abeta. Here we show that systemic administration of physostigmine, an acetylcholinesterase inhibitor, lowers Abeta levels in vivo. Guinea pigs treated for 10 days with s.c. physostigmine had levels of cortical AbetaN-40 and N-42 which were 57% and 72%, respectively, of those in control animals. Levels of cortical beta-amyloid precursor protein were not significantly affected by drug treatment. These results suggest that cholinergic therapy may affect the course of AD by limiting Abeta accumulation.
Beach
T G
TG
Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85372, USA. tbeach@mail.sunhealth.org
Kuo
Y M
YM
Schwab
C
C
Walker
D G
DG
Roher
A E
AE
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D010830:Physostigmine / Q000008:administration & dosage / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D010830:Physostigmine