Heterogeneity of water-soluble amyloid beta-peptide in Alzheimer's disease and Down's syndrome brains

FEBS Lett. 1997 Jun 16;409(3):411-6. doi: 10.1016/s0014-5793(97)00564-4.

Abstract

Water-soluble amyloid beta-peptides (sA beta), ending at residue 42, precede amyloid plaques in Down's syndrome (DS). Here we report that sA beta consists of the full-length A beta(1-42) and peptides truncated and modified by cyclization of the N-terminal glutamates, A beta[3(pE)-42] and A beta[11(pE)-42]. The A beta[3(pE)-42] peptide is the most abundant form of sA beta in Alzheimer's disease (AD) brains. In DS, sA beta[3(pE)-42] concentration increases with age and the peptide becomes a dominant species in the presence of plaques. Both pyroglutamate-modified peptides and the full-length A beta form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sA beta in the plaque formation and pathogenesis of AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Cerebral Cortex / chemistry*
  • Chromatography, Gel
  • Down Syndrome / metabolism*
  • Electrophoresis, Agar Gel
  • Humans
  • Immunochemistry
  • Pyrrolidonecarboxylic Acid
  • Solubility
  • Water

Substances

  • Amyloid beta-Peptides
  • Water
  • Pyrrolidonecarboxylic Acid