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.
Fonseca
M I
MI
Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, California, 92697, USA.
Head
E
E
Velazquez
P
P
Cotman
C W
CW
Tenner
A J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D000906:Antibodies; D001224:Aspartic Acid / Q000032:analysis*; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D004314:Down Syndrome / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009928:Organ Specificity; D058225:Plaque, Amyloid / Q000473:pathology*; D012044:Regression Analysis
D000906:Antibodies; D015415:Biomarkers; D001224:Aspartic Acid