Affiliation:
1. Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada
Abstract
Background:
In Alzheimer’s disease (AD), and amyloid models such as the 5XFAD
mouse, butyrylcholinesterase (BChE) is associated with β-amyloid (Aβ) plaques and has unique
biochemical features which distinguish it from that found in neurons. It has been suggested that
BChE associated with Aβ plaques may be involved in the maturation of this structure and thus disease
progression.
Objective:
Currently, it is unknown whether BChE bound to Aβ plaques has altered biochemical
properties due to a different primary structure or because of the association of this enzyme with Aβ
plaques. Also, the source and binding mechanism of this BChE remains unknown.
Methods:
Brain tissue sections from the 5XFAD/BChE-KO mouse were incubated with exogenous
sources of BChE and stained for this enzyme’s activity. Efforts were made to determine what region
of BChE or Aβ may be involved in this association.
Results:
We found that incubation of 5XFAD/BChE-KO brain tissues with exogenous BChE led to
this enzyme becoming associated with Aβ plaques and neurons. In contrast to neuronal BChE, the
BChE bound to Aβ plaques had similar biochemical properties to those seen in AD. Mutations to
BChE and efforts to block Aβ epitomes failed to prevent this association.
Conclusion:
The association of BChE with Aβ plaques, and the resultant biochemical changes,
suggests that BChE may undergo a conformational change when bound to Aβ plaques but not neurons.
The 5XFAD/BChE-KO model is ideally suited to explore the binding mechanism of BChE to
Aβ plaques as well as the involvement of BChE in AD pathogenesis.
Funder
Canadian Institutes of Health Research
Publisher
Bentham Science Publishers Ltd.
Subject
Neurology (clinical),Neurology
Cited by
5 articles.
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