| Summary: | Background: Butyrylcholinesterase (BChE), also known as the “pseudo” or “non-neuronal” cholinesterase, is traditionally thought to have a restricted CNS distribution and to play little, if any, role in cholinergic transmission. Objective: To reanalyze the role of BChE in the human brain with more sensitive methodology. Methods: Three brains were examined with acetylcholinesterase and BChE histochemistry. The sections were examined with bright- and dark-field microscopy. Results: The histochemical parameters used in the present experiments showed that BChE activity was present in all hippocampal and temporal neocortical areas known to receive cholinergic input. At all of these locations, the BChE enzyme could hydrolyze the acetylcholine surrogate acetylthiocholine. A substantial portion of the hippocampal and neocortical BChE appeared to be located within neuroglia and their processes. Conclusions: Butyrylcholinesterase may have a greater role in cholinergic transmission than previously surmised, making BChE inhibition an important therapeutic goal in Alzheimer's disease. The results also suggest that the role of neuroglia in cholinergic transmission may be analogous to their well known role in glutamatergic transmission.
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