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

Background: In Alzheimer's disease (AD), and amyloid models such as the 5XFAD mouse, butyrylcholinesterase (BChE) is associated with beta-amyloid (A beta) plaques and has unique biochemical features which distinguish it from that found in neurons. It has been suggested that BChE associated with A beta plaques may be involved in the maturation of this structure and thus disease progression. Objective: Currently, it is unknown whether BChE bound to A beta plaques has altered biochemical properties due to a different primary structure or because of the association of this enzyme with A beta 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 A beta 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 A beta plaques and neurons. In contrast to neuronal BChE, the BChE bound to A beta plaques had similar biochemical properties to those seen in AD. Mutations to BChE and efforts to block A beta epitomes failed to prevent this association. Conclusion: The association of BChE with A beta plaques, and the resultant biochemical changes, suggests that BChE may undergo a conformational change when bound to A beta plaques but not neurons. The 5XFAD/BChE-KO model is ideally suited to explore the binding mechanism of BChE to A beta plaques as well as the involvement of BChE in AD pathogenesis.