CHOLINESTERASE-INHIBITORS INCREASE SECRETION OF APPS IN RAT-BRAIN CORTEX

WE examined whether cholinesterase inhibitors (ChEI) could alter the r elease of amyloid precursor protein (APP) from superfused brain cortic al slices of the rat. Three ChEI, both reversible and irreversible, we re tested for their ability to enhance the release of nonamyloidogenic soluble derivatives (APPs). These included: physostigmine (PHY), hept yl-physostigmine (HEP) and 2,2-dichlorovinyldimethyl phosphate (DDVP), at concentrations producing cholinesterase (ChE) inhibition ranging f rom 5% to 95%. All three ChEI elevated APPs release significantly abov e control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed afte r muscarinic receptor stimulation with bethanechol (BETHA). Tetrodotox in (TTX) completely blocked the effect of electrical stimulation. Thes e findings suggest that administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal A PP processing.