Elevated aβ levels in Alzheimer's disease brain are associated with selective accumulation of aβ42 in parenchymal amyloid plaques and both aβ40 and aβ42 in cerebrovascular deposits

Mary J. Savage, John K. Kawooya, Leonard R. Pinsker, Thomas L. Emmons, Suzanne Mistretta, Robert Siman, Barry D. Greenberg

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)234-240
Number of pages7
JournalAmyloid
Volume2
Issue number4
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Keywords

  • Alzheimer
  • Amyloid
  • Aβ protein
  • Electrophoresis
  • Senile plaques

ASJC Scopus subject areas

  • Internal Medicine

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