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Neuroglial cholinesterases in the normal brain and in Alzheimer's disease: Relationship to plaques, tangles, and patterns of selective vulnerability
Author(s) -
Wright Christopher I.,
Geula Changiz,
Mesulam M.Marsel
Publication year - 1993
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410340312
Subject(s) - butyrylcholinesterase , acetylcholinesterase , entorhinal cortex , white matter , alzheimer's disease , cholinesterase , cerebral cortex , neuroglia , pathology , somatosensory system , neuroscience , aché , chemistry , biology , endocrinology , hippocampus , central nervous system , enzyme , biochemistry , medicine , disease , magnetic resonance imaging , radiology
Butyrylcholinesterase (BChE) and an altered form of acetylcholinesterase (AChE) accumulate in the plaques and tangles of Alzheimer's disease (AD). The sources for these plaque‐ and tangle‐bound cholinesterases have not been identified. We now report that AChE and BChE activities with pH preferences and inhibitor selectivities identical to those of plaque‐ and tangle‐bound cholinesterases are found in the astrocytes and oligodendrocytes of control and AD brains. These glial‐type cholinesterases are selectively inhibited by indolamines and protease inhibitors. In control brains glial‐type cholinesterases appear confined to the intracellular space, whereas in patients with AD they decorate plaques and tangles as well. In control and AD brains AChE‐positive glia are distributed throughout the cortical layers and subcortical white matter, whereas BChE‐positive glia reach high densities only in the deep cortical layers and white matter. In non‐AD control brains, the ratio of BChE to AChE glia was higher in entorhinal and inferotemporal cortex, two regions with a high susceptibility to the pathology of AD, than in primary somatosensory and visual cortex, two areas with a relatively lower susceptibility to the disease process. There were no age‐related differences in the density or distribution of cholinesterase‐positive glia. In comparison with age‐matched control specimens, AD brains had a significantly higher density of BChE glia and a lower density of AChE glia in entorhinal and inferotemporal regions but not in the primary somatosensory or visual areas. These results suggest that glia constitute a likely source for the cholinesterase activity of plaques and tangles and that a high ratio of BChE‐ to AChE‐positive glia may play a permissive or causative role in the neuropathology of AD.