title: Butyrylcholinesterase in the life cycle of amyloid plaques.
abstract: Deposits of diffuse beta-amyloid (Abeta) may exist in the brain for many years before leading to neuritic degeneration and dementia. The factors that contribute to the putative transformation of the Abeta amyloid from a relatively inert to a pathogenic state remain unknown and may involve interactions with additional plaque constituents. Matching brain sections from 2 demented and 4 nondemented subjects were processed for the demonstration of Abeta immunoreactivity, butyrylcholinesterase (BChE) enzyme activity, and thioflavine S binding. Additional sections were processed for the concurrent demonstration of two or three of these markers. A comparative analysis of multiple cytoarchitectonic areas processed with each of these markers indicated that Abeta plaque deposits are likely to undergo three stages of maturation, ie, a "diffuse" thioflavine S-negative stage, a thioflavine S-positive (ie, compact) but nonneuritic stage, and a compact neuritic stage. A multiregional analysis showed that BChE-positive plaques were not found in cytoarchitectonic areas or cortical layers that contained only the thioflavine S-negative, diffuse type of Abeta plaques. The BChE-positive plaques were found only in areas containing thioflavine S-positive compact plaques, both neuritic and nonneuritic. Within such areas, almost all (>98%) BChE-containing plaques bound thioflavine S, and almost all (93%) thioflavine S plaques contained BChE. These results suggest that BChE becomes associated with amyloid plaques at approximately the same time that the Abeta deposit assumes a compact beta-pleated conformation. BChE may therefore participate in the transformation of Abeta from an initially benign form to an eventually malignant form associated with neuritic tissue degeneration and clinical dementia.
authors.affiliation: Cognitive Neurology and Alzheimer Disease Center, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Guillozet
authors.forename: J F
authors.initials: JF
authors.lastname: Smiley
authors.forename: D C
authors.initials: DC
authors.lastname: Mash
authors.forename: M M
authors.initials: MM
authors.lastname: Mesulam
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology; D052160:Benzothiazoles; D002091:Butyrylcholinesterase / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000201:enzymology*; D013702:Temporal Lobe / Q000201:enzymology; D013844:Thiazoles
chemical_list: D052160:Benzothiazoles; D005456:Fluorescent Dyes; D013844:Thiazoles; C009462:thioflavin T; D002091:Butyrylcholinesterase