In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease synapses
Kuhl, David E.; Koeppe, Robert A.; Snyder, Scott E.; Minoshima, Satoshi; Frey, Kirk A.; Kilbourn, Michael R.
2006-01
Citation
Kuhl, David E.; Koeppe, Robert A.; Snyder, Scott E.; Minoshima, Satoshi; Frey, Kirk A.; Kilbourn, Michael R. (2006)."In vivo butyrylcholinesterase activity is not increased in Alzheimer's disease synapses." Annals of Neurology 59(1): 13-20. <http://hdl.handle.net/2027.42/49279>
Abstract
Objective We tested the premise that cholinesterase inhibitor therapy should target butyrylcholinesterase (BuChE) in Alzheimer's disease (AD), not acetylcholinesterase (AChE) alone, because both enzymes hydrolyze acetylcholine, and BuChE is increased in AD cerebral cortex. Methods To examine this issue in vivo, we quantified human cerebral cortical BuChE activity using tracer kinetic estimates (k 3 ) of 1-[ 11 C]methyl-4-piperidinyl n-butyrate ([ 11 C]BMP) hydrolysis determined by positron emission tomography. Validation of the putative positron emission tomography method included regional distribution, positive correlation with age, and attenuation by the nonselective cholinesterase inhibitor physostigmine, but no attenuation by the AChE-selective inhibitor donepezil. Positron emission tomography scans in AD patients (n = 15) and control subjects (n = 12) measured both BuChE (using [ 11 C]BMP) and AChE activity (using N-[ 11 C] methylpiperidin-4-yl propionate, an established method). Results As expected, AChE activity in AD cerebral cortex was decreased to 75 ± 13% of normal ( p = 0.00001). Contrary to prediction, accompanying BuChE activity also was decreased to 82 ± 14% of normal ( p = 0.001). Interpretation Failure to observe increased [ 11 C]BMP hydrolysis in vivo makes it less likely that incremental BuChE contributes importantly to acetylcholine hydrolysis in AD. The findings do not support the premise that inhibitor therapy should target BuChE so as to prevent increased levels of BuChE from hydrolyzing acetylcholine in AD cerebral cortex. Ann Neurol 2006Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0364-5134 1531-8249
Other DOIs
PMID
16278840
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16278840&dopt=citationMetadata
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