Molecular Forms of Acetylcholinesterase and Butyrylcholinesterase in the Aged Human Central Nervous System

Abstract

The distributions of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) molecular forms and their solubility characteristics were examined, using density gradient centrifugation, in various regions of the postmortem human CNS. Total AChE activity varied extensively (50-fold) among the regions investigated, being highest in the telencephalic subcortical structures (caudate nucleus and nucleus of Meynert); intermediate in the substantia nigra, cerebellum, and spinal cord; and least in the fornix and cortical regions (hippocampus and temporal and parietal cortex). Total BChE activity was, in contrast, much more evenly distributed, with only a threefold variation between the regions studied. Although the patterns of molecular forms of each enzyme were broadly similar among the different areas, regional variations in the distribution and abundance of the various forms of AChE were much greater than those of BChE. Thus, although the tetrameric G4 form of AChE constituted the majority of the total AChE activity in all regions examined, the ratio of the G4 form to the monomeric G1 form, the latter of which constituted the majority of the remaining activity, varied markedly, ranging from 21 in the caudate nucleus to 1.7 in the tem-poral cortex. In addition to the G4 and GI forms of AChE, the dimeric G2 form was observed in the nucleus of Meynert and a fast-sedimenting (16s) species was found in samples of both the parietal cortex and spinal cord. In contrast, the G4 and GI forms of BChE were the only molecular species observed in the different areas and the G4:Gl ratio varied from 3.3 in the substantia nigra to 0.9 in the temporal cortex. Regarding the solubility characteristics of the individual AChE and BChE molecular forms, the majority of the G4 form of AChE was extractable only in the presence of detergent, indicating a predominantly membrane-bound localization of this species. The smaller AChE forms (GI and G2) and both the G I and G4 forms of BChE were all relatively evenly distributed between soluble and membrane-bound species. These findings are discussed in relation to neurochemical and neuroanatomical, particularly cholinergic, features of the regions examined.

Blood Cells Cholinesterase Activity in Early Stage Alzheimer’s Disease and Vascular Dementia

“…However, in most cases the decrease did not have statistical significance when the level of significance was corrected for multiple comparisons. There are reports showing increase of BuChE activity associated to decreased AChE in AD patients [20,[32][33][34]. Increased BuChE activity could be a compensatory mechanism to substitute for AChE, although BuChE activity in the brain appears to be constitutive (rather than compensatory) in AChE knockout mice [19].…”

Rosemary tea consumption results to anxiolytic- and anti-depressant-like behavior of adult male mice and inhibits all cerebral area and liver cholinesterase activity; phytochemical investigation and in silico studies

“…In the SS fraction the cytosolic G1 isoform of the AChE predominates, whereas the DS fraction contains mainly the membrane-bound G4 isoform of the enzyme. G1 and G4 isoforms of BChE are evenly distributed in between soluble and membrane-bound species [35], thus none of them predominates in the fractions.…”

Evaluation of Simplified Kinetic Analyses for Measurement of Brain Acetylcholinesterase Activity Using N-[11C]Methylpiperidin-4-yl Propionate and Positron Emission Tomography

“…There is a large difference in AChE activity across brain regions; the interrelation of temporal cortex/thalamus/cerebellum/striatal AChE activities is 1/3/8/38, as determined in normal brain postmortem (Atack et al, 1986;Arai et al, 1984). In this […”