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Distribution of the molecular forms of acetylcholinesterase in human brain: Alterations in dementia of the Alzheimer type
Author(s) -
Fishman Eric B.,
Siek Gordon C.,
MacCallum Robert D.,
Bird Edward D.,
Volicer Ladislav,
Marquis Judith K.
Publication year - 1986
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.410190305
Subject(s) - acetylcholinesterase , dementia , alzheimer's disease , neuroscience , human brain , distribution (mathematics) , medicine , psychology , biology , pathology , disease , biochemistry , enzyme , mathematical analysis , mathematics
Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, is a heterogeneous enzyme that can be separated into multiple molecular forms. A tetrameric membrane‐bound form (G 4 ) and a monomeric soluble form (G 1 ) are the two predominant enzyme species in mammalian brain. The distribution of AChE molecular forms was defined by sucrose density gradients of 11 anatomical regions of postmortem brains from 10 patients with dementia of the Alzheimer type (DAT) and 14 nondemented controls of similar ages. The results demonstrate an overall loss of protein and enzyme activity in all areas of the DAT brains studied and a selective loss of the G 4 form of AChE in Brodmann areas 9, 10, 11, 21, 22, and 40, and the amygdala. There was no change in the G 4 /G 1 ratio in areas 17 and 20, in the hippocampus, or in the cerebellum. There was a high regional correlation of the G 4 /G 1 ratios with published values for choline acetyltransferase activity but lower correlation with total AChE activity. We propose that there is a predominant loss of the G 4 form of AChE in DAT and that this loss is correlated with the degeneration of presynaptic elements.