Butyrylcholinesterase in the life cycle of amyloid plaques

Deposits of diffuse β‐amyloid (Aβ) 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 Aβ amyloid from a relatively inert to a pathogenic state remain unknown and may involve interactions with additional plaque consituents. Matching brain sections from 2 demented and 4 nondemented subjects were processed for the demonstration of Aβ immunoreactivity, butyrylchlinesterase (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 Aβ 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 Aβ 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 Aβ deposit assumes a compact β‐pleated conformation. BChE may therefore participate in the transformation of Aβ from an initially benign form to an eventually malignant form associated with neuritic tissue degeneration and clinical dementia.