The presence of isoaspartic acid in beta-amyloid plaques indicates plaque age.

Extracellular deposits of fibrillar beta-amyloid are a characteristic neuropathology of Alzheimer's disease (AD). We have developed a novel antibody to a hypothesized "older isomer" of the amyloid protein. This antibody, raised against a synthetic beta-amyloid peptide containing isoaspartic acid at position 7 (isoaspartic-7-Abeta), reacts with isoaspartic-7-Abeta, a nonenzymatic modification found in long-lived proteins. Plaques stained with this antibody are thioflavine positive and are found throughout the frontal and entorhinal cortices of AD cases. In frontal cortex, isoaspartic-7-Abeta plaques are clustered but have a widespread distribution in all cortical layers. Isoaspartic-7-Abeta is found primarily in the core of individual plaques surrounded by nonisomerized amyloid. Activated microglia are associated with plaques containing isomerized and nonisomerized amyloid. In contrast to AD, isoaspartic-7-Abeta plaques in Down's syndrome (DS) cases are found primarily in the superficial layers of frontal cortex. Using image analysis isoaspartic-7-Abeta deposition was correlated with dementia severity in AD and with age in DS. The results indicate that this antibody against altered aspartyl amyloid could be a useful indicator of the age of amyloid plaques.
AuthorsM I Fonseca, E Head, P Velazquez, C W Cotman, A J Tenner
JournalExperimental neurology (Exp Neurol) Vol. 157 Issue 2 Pg. 277-88 (Jun 1999) ISSN: 0014-4886 [Print] UNITED STATES
PMID10364440 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 1999 Academic Press.
Chemical References
  • Antibodies
  • Biomarkers
  • Aspartic Acid
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Alzheimer Disease (pathology, physiopathology, psychology)
  • Antibodies
  • Aspartic Acid (analysis)
  • Autopsy
  • Biomarkers (analysis)
  • Brain (growth & development, pathology)
  • Down Syndrome (pathology, physiopathology, psychology)
  • Entorhinal Cortex (pathology)
  • Female
  • Frontal Lobe (pathology)
  • Humans
  • Immunohistochemistry
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Organ Specificity
  • Plaque, Amyloid (pathology)
  • Regression Analysis

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