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Alzheimer amyloid β/A4 peptide binding sites and a possible 'APP-secretase' activity associated with rat brain cortical membranes

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  • D Allsop
  • T Yamamoto
  • F Kametani
  • N Miyazaki
  • T Ishii
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<mark>Journal publication date</mark>14/06/1991
<mark>Journal</mark>Brain Research
Issue number1-2
Volume551
Number of pages9
Pages (from-to)1-9
Publication statusPublished
Original languageEnglish

Abstract

We carried out ligand binding experiments on membranes from rat brain cortical grey matter using radioiodinated beta/A4 8-17, with non-specific binding determined by the addition of 10 microM unlabelled peptide. Specific, reversible binding amounted to 60-75% of total binding and showed a clear dependence on time, temperature, pH and membrane concentration. Kinetic analyses indicated a high-affinity binding site with an apparent KD of 440 pM. However, the ligand was partly degraded with loss of the Ser8, Lys16 and Leu17 residues. Excision of the two C-terminal amino acids was inhibited by EDTA, EGTA, dithiothreitol or Zn2+ but was stimulated by Ca2+ or Mn2+. These studies demonstrate high-affinity binding sites for beta/A4 8-17 (or its derivatives) in rat brain, suggesting that this region may contain a physiologically important amino acid sequence and identify a potential membrane-associated amyloid precursor protein (APP) secretase activity.