Full-length amyloid-beta (1-42(43)) and amino-terminally modified and truncated amyloid-beta 42(43) deposit in diffuse plaques

Am J Pathol. 1996 Dec;149(6):1823-30.


The amino- and carboxyl-terminal properties of the amyloid-beta (A beta) peptides deposited in diffuse plaques, one of the earliest forms of A beta deposition, were examined in the brains of patients with Down's syndrome and Alzheimer's disease and in aged individuals without dementia by immunocytochemistry. This was done using a panel of antibodies that specifically discriminate the terminal structures and modifications at the amino and carboxyl termini of A beta. Diffuse plaques found in the cerebral and cerebellar cortex, neostriatum, and hypothalamus of Down's syndrome, Alzheimer's disease, and nondemented brains were strongly immunoreactive for A beta N1(L-Asp), A beta N1(L-isoAsp), A beta N1(D-Asp), and A beta N3(pyroGlu) and weakly positive for A beta N11(pyroGlu) and A beta N17(Leu). Diffuse plaques also were positive for A beta 42(43) but negative for A beta 40, using carboxyl-terminal-specific anti-A beta antibodies. These results suggest that the amino termini of the A beta species that initially deposit in diffuse plaques begin with A beta N1(Asp) with or without structural modifications (isomerization and racemization), as well as with A beta N3(pyroGlu), and terminate preferentially at A beta 42(43) rather than A beta 40.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Down Syndrome / metabolism
  • Down Syndrome / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neurofibrillary Tangles / metabolism*
  • Neurofibrillary Tangles / pathology*
  • Sequence Deletion*


  • Amyloid beta-Peptides