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. 1993 Jun;13(3):279–287. doi: 10.1007/BF00733756

Proteolysis at the secretase and amyloidogenic cleavage sites of theβ-amyloid precursor protein by acetylcholinesterase and butyrylcholinesterase using model peptide substrates

M de Serres 1,✉, D Sherman 3, W Chestnut 3, B M Merrill 3, O H Viveros 3, E J Diliberto Jr 1
PMCID: PMC11566965  PMID: 8242691

Abstract

  1. It was recently proposed that acetylcholinesterase (AChE), in addition to its esteratic activity, has proteolytic activity such that it may cleave theβ-amyloid precursor (β-APP) within theβ-amyloid sequence. The purpose of this paper was to examine further whether AChE or butyrylcholinesterase (BuChE) had associated proteinase activity that was involved in the metabolism ofβ-APP.

  2. The ability of various preparations of AChE and BuChE to hydrolyze two synthetic fragments ofβ-APP695 as model substrates containing the normal and aberrant cleavage sites was studied.

  3. Digestion of these synthetic substrates with commercial preparations ofElectrophorus electricus AChE indicated the presence of a trypsin-like proteolytic activity cleaving each peptide at the carboxy-terminal side of an internal lysine residue.

  4. Purification of the trypsin-like proteinase activity by aminobenzamidine affinity chromatography yielded a preparation that was devoid of AChE activity but retained all of the proteinase activity.

  5. Amino-terminal sequence analysis of this preparation showed that the first 13 amino acid residues were identical toβ-pancreatic trypsin.

  6. These data indicate that the proteinase activity found in these commercial preparations of AChE is due to contamination with trypsin.

Key words: Alzheimer's disease, β-amyloid precursor protein, acetylcholinesterase, β/A4 peptide, secretase, amyloidosis

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