TY - JOUR
T1 - Rivastigmine is a potent inhibitor of acetyl- and butyrylcholinesterase in Alzheimer's plaques and tangles
AU - Eskander, Mariam F.
AU - Nagykery, Nicholas G.
AU - Leung, Elaine Y.
AU - Khelghati, Bahiyyih
AU - Geula, Changiz
PY - 2005/10/26
Y1 - 2005/10/26
N2 - Acetylcholinesterase and butyrylcholinesterase activities emerge in association with plaques and tangles in Alzheimer's disease. These pathological cholinesterases, with altered properties, are suggested to participate in formation of plaques. The present experiment assessed the ability of rivastigmine, a clinically utilized agent that inhibits acetylcholinesterase and butyrylcholinesterase activities, to inhibit cholinesterases in plaques and tangles. Cortical sections from cases of Alzheimer's disease were processed using cholinesterase histochemistry in the presence or absence of rivastigmine. Optical densities of stained sections were utilized as a measure of inhibition. The potency of rivastigmine was compared with those of other specific inhibitors. Optimum staining for cholinesterases in neurons and axons was obtained at pH 8.0. Cholinesterases in plaques, tangles and glia were stained best at pH 6.8. Butyrylcholinesterase-positive plaques were more numerous than acetylcholinesterase-positive plaques. Rivastigmine inhibited acetylcholinesterase in all positive structures in a dose-dependent manner (10-6-10-4 M). However, even at the highest concentration, faint activity remained. In contrast, rivastigmine resulted in complete inhibition of butyrylcholinesterase in all structures at 10-5 M. Rivastigmine was equipotent to the specific acetylcholinesterase inhibitor BW284C51 and more potent than the butyrylcholinesterase inhibitors iso-OMPA and ethopropazine. In conclusion, rivastigmine is a potent inhibitor of acetylcholinesterase and a more potent inhibitor of butyrylcholinesterase in plaques and tangles. Unlike other cholinesterase inhibitors tested, rivastigmine inhibited cholinesterases in normal and pathological structures with the same potency. Thus, at the therapeutic concentrations used, rivastigmine is likely to result in inhibition of pathological cholinesterases, with the potential of interfering with the disease process.
AB - Acetylcholinesterase and butyrylcholinesterase activities emerge in association with plaques and tangles in Alzheimer's disease. These pathological cholinesterases, with altered properties, are suggested to participate in formation of plaques. The present experiment assessed the ability of rivastigmine, a clinically utilized agent that inhibits acetylcholinesterase and butyrylcholinesterase activities, to inhibit cholinesterases in plaques and tangles. Cortical sections from cases of Alzheimer's disease were processed using cholinesterase histochemistry in the presence or absence of rivastigmine. Optical densities of stained sections were utilized as a measure of inhibition. The potency of rivastigmine was compared with those of other specific inhibitors. Optimum staining for cholinesterases in neurons and axons was obtained at pH 8.0. Cholinesterases in plaques, tangles and glia were stained best at pH 6.8. Butyrylcholinesterase-positive plaques were more numerous than acetylcholinesterase-positive plaques. Rivastigmine inhibited acetylcholinesterase in all positive structures in a dose-dependent manner (10-6-10-4 M). However, even at the highest concentration, faint activity remained. In contrast, rivastigmine resulted in complete inhibition of butyrylcholinesterase in all structures at 10-5 M. Rivastigmine was equipotent to the specific acetylcholinesterase inhibitor BW284C51 and more potent than the butyrylcholinesterase inhibitors iso-OMPA and ethopropazine. In conclusion, rivastigmine is a potent inhibitor of acetylcholinesterase and a more potent inhibitor of butyrylcholinesterase in plaques and tangles. Unlike other cholinesterase inhibitors tested, rivastigmine inhibited cholinesterases in normal and pathological structures with the same potency. Thus, at the therapeutic concentrations used, rivastigmine is likely to result in inhibition of pathological cholinesterases, with the potential of interfering with the disease process.
KW - Acetylcholinesterase
KW - Alzheimer
KW - Butyrylcholinesterase
KW - Plaque
KW - Rivastigmine
KW - Tangle
UR - http://www.scopus.com/inward/record.url?scp=26944456359&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=26944456359&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2005.08.039
DO - 10.1016/j.brainres.2005.08.039
M3 - Article
C2 - 16212945
AN - SCOPUS:26944456359
VL - 1060
SP - 144
EP - 152
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -