Amino- and carboxyl-terminal heterogeneity of beta-amyloid peptides deposited in human brain

Neurosci Lett. 1996 Sep 13;215(3):173-6. doi: 10.1016/0304-3940(96)12970-0.


We aimed to determine quantitatively the fine amino- and carboxyl-terminal structure of A beta peptides deposited in human brain using a set of 12 anti-A beta antibodies that distinguish between terminal modifications including isomerization, stereoisomerization, limited proteolysis, and cyclization. Immunochemical examination of cortical blocks from aged subjects distinguished by their total plaque load and from a young Down's syndrome patient identified the major invariantly deposited species as A beta x-42 (X = 1(D-aspartate) and 3(pyroglutamate) and/or 11(pyroglutamate)). These molecular forms, presumably representing by-products of metabolic intermediates toward degradation, are similar in being resistant to major aminopeptidases. A beta 17-42 ("p3' fragment), a major secreted form of truncated A beta with high insolubility, was found to be a minor one. A possible interpretation for these observations would be that proteolysis of A beta from its amino terminus may limit the rate of A beta catabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / metabolism*
  • Blotting, Western
  • Brain / metabolism*
  • Humans


  • Amyloid beta-Protein Precursor