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 constituents. Matching brain sections from 2 demented and 4 nondemented subjects were processed for the demonstration of Aβ 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 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.