Abstract
Amyloid deposits in Alzheimer's disease (AD) brains are composed primarily of the protein Aβ a proteolytic fragment of the βamyloid precursor protein. Antibodies were generated to peptides corresponding to the five COOH-terminal residues of Aβ proteins ending either at residue 40 (anti-Aβ36-40) or 42 (anti-Aβ 38-42). The selectivity of these antibodies for their respective peptides was determined by antibody preabsorption followed by ELISA or immunohistochemistry. Anti-Aβ38-42 labeled core-containing and diffuse plaques in both frozen and paraffin sections. Anti-Aβ36-40 labeled a smaller number of core-containing plaques and no diffuse plaques. Vascular and perivascular amyloid contained Aβ proteins ending both at residue 40 and 42. Forms ending at residue 40 comprised a larger fraction of both vascular and perivascular amyloid compared to parenchymal amyloid, suggesting that parenchymal amyloid and vascular/perivascular amyloid are derived by two distinct mechanisms. In addition, Aβ proteins immunoaffinity purified from plaque-enriched human brains were resolved by a novel electrophoretic method into two predominant forms, co-migrating with synthetic Aβ1-40and Aβ1-42. The quantity of Aβ protein solubilized from AD brains was greater than that from age-matched controls, demonstrating a preferential accumulation of this soluble Aβ in association with amyloid deposition. Our results demonstrate immunohistochemical and electrophoretic methods for defining further the processes contributing to Aβ amyloidogenesis.
Original language | English (US) |
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Pages (from-to) | 234-240 |
Number of pages | 7 |
Journal | Amyloid |
Volume | 2 |
Issue number | 4 |
DOIs | |
State | Published - 1995 |
Externally published | Yes |
Keywords
- Alzheimer
- Amyloid
- Aβ protein
- Electrophoresis
- Senile plaques
ASJC Scopus subject areas
- Internal Medicine