The Presence of Isoaspartic Acid in β-Amyloid Plaques Indicates Plaque Age

• Published in: Experimental neurology 1999-06, Vol.157 (2), p.277-288
• Main Authors: Fonseca, Maria I., Head, Elizabeth, Velazquez, Peter, Cotman, Carl W., Tenner, Andrea J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aging; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Alzheimer Disease - psychology; Alzheimer's disease; Antibodies; Aspartic Acid - analysis; Autopsy; Aβ plaques; Biological and medical sciences; Biomarkers - analysis; Brain - growth & development; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Down Syndrome - pathology; Down Syndrome - physiopathology; Down Syndrome - psychology; Down's syndrome; Entorhinal Cortex - pathology; Female; Frontal Lobe - pathology; Humans; Immunohistochemistry; isoaspartic-7-Aβ plaques; Male; Medical sciences; Mental Status Schedule; Middle Aged; Neurology; Organ Specificity; Plaque, Amyloid - pathology; Regression Analysis
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1999.7058

Extracellular deposits of fibrillar β-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 β-amyloid peptide containing isoaspartic acid at position 7 (isoaspartic-7-Aβ), reacts with isoaspartic-7-Aβ, 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-Aβ plaques are clustered but have a widespread distribution in all cortical layers. Isoaspartic-7-Aβ 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-Aβ plaques in Down's syndrome (DS) cases are found primarily in the superficial layers of frontal cortex. Using image analysis isoaspartic-7-Aβ 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.