Interaction of Exogenous Butyrylcholinesterase with β-Amyloid Plaques in 5XFAD/Butyrylcholinesterase-Knockout Mouse Brain

Author(s): G.A. Reid, S. Darvesh*

Journal Name: Current Alzheimer Research

Volume 18 , Issue 6 , 2021


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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.

Keywords: Butyrylcholinesterase, β-amyloid plaques, 5XFAD, neurodegeneration, Alzheimer's disease, Karnovsky-Roots histochemistry.

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Article Details

VOLUME: 18
ISSUE: 6
Year: 2021
Published on: 27 August, 2021
Page: [470 - 481]
Pages: 12
DOI: 10.2174/1567205018666210827122704
Price: $65

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