Human recombinant butyrylcholinesterase purified from the milk of transgenic goats interacts with beta-amyloid fibrils and suppresses their formation in vitro

E. Podoly, T. Bruck, S. Diamant, N. Melamed-Book, A. Weiss, Y. Huang, O. Livnah, S. Langermann, H. Wilgus, H. Soreq

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background: In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co-localizes with β-amyloid (Aβ) fibrils. Aims: In vitro testing of the significance of this phenomenon to AD progress. Methods: A thioflavine T (ThT) fluorogenic assay, photo-induced cross-linking and quantifiable electron microscopy served to compare the effect on Aβ fibril formation induced by highly purified recombinant human BChE (rBChE) produced in the milk of transgenic goats with that of serum-derived human BChE. Results: Both proteins at 1:50 and 1:25 ratios to Aβ dose-dependently prolonged the ThT lag time and reduced the apparent rate of Aβ fibril formation compared to Aβ alone. Photo-induced cross-linking tests showed that rBChE prolonged the persistence of amyloid dimers, trimers and tetramers in solution, whereas Aβ alone facilitated precipitation of such multimers from solution. Transmission electron microscopy showed that rBChE at 1:100 to Aβ prevented the formation of larger, over 150-nm-long, Aβ fibrils and reduced fibril branching compared to Aβ alone as quantified by macro programming of Image Pro® Plus software. Conclusion: Our findings demonstrate that rBChE interacts with Aβ fibrils and can attenuate their formation, extension and branching, suggesting further tests of rBChE, with unlimited supply and no associated health risks, as a therapeutic agent for delaying the formation of amyloid toxic oligomers in AD patients.

Original languageEnglish
Pages (from-to)232-236
Number of pages5
JournalNeurodegenerative Diseases
Volume5
Issue number3-4
DOIs
StatePublished - Mar 2008

Keywords

  • Alzheimer's disease
  • Human recombinant butyrylcholinesterase
  • β-Amyloid

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