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Isoaspartate formation at position 23 of amyloid beta peptide enhanced fibril formation and deposited onto senile plaques and vascular amyloids in Alzheimer's disease.

Abstract
Senile plaques and amyloid-bearing vessels consisting of fibrillar amyloid beta peptides (A beta) are characteristic neuropathological features of Alzheimer's disease (AD). A beta undergo spontaneous post-translational modifications, such as isomerization and racemization, at their aspartyl residues in AD brains. Here we present evidence that A beta isomerized at position 23 are deposited on plaques and vascular amyloids using an anti-isomerized A beta antibody. In vitro experiments showed that isomerization at position 23, but not position 7, enhanced aggregation. Furthermore, A beta with the Dutch mutation, but not the Flemish mutation, also showed greatly enhanced aggregation. These results suggest that mutations or modifications at positions Glu 22 and Asp 23 have a pathogenic role in the deposition of A beta. The development and progression of sporadic AD may be accelerated by spontaneous isomerization at position 23 of A beta.
AuthorsTakahiko Shimizu, Hiroyuki Fukuda, Shigeo Murayama, Naoki Izumiyama, Takuji Shirasawa
JournalJournal of neuroscience research (J Neurosci Res) Vol. 70 Issue 3 Pg. 451-61 (Nov 1 2002) ISSN: 0360-4012 [Print] United States
PMID12391606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2002 Wiley-Liss, Inc.
Chemical References
  • Amyloid beta-Peptides
  • Aspartic Acid
Topics
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease (genetics, metabolism, pathology)
  • Amino Acid Sequence
  • Amyloid beta-Peptides (genetics, metabolism)
  • Aspartic Acid (metabolism)
  • Blood Vessels (metabolism, pathology, physiopathology)
  • Brain (metabolism, pathology, physiopathology)
  • Female
  • Humans
  • Immunohistochemistry
  • Isomerism
  • Male
  • Microscopy, Electron
  • Molecular Structure
  • Neurofibrillary Tangles (metabolism, pathology, ultrastructure)
  • Plaque, Amyloid (metabolism, pathology, ultrastructure)

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