Enhanced binding of advanced glycation endproducts (age) by apo e4 isotype linkt mechanisms of plaque deposition in alzheimer's disease

Y. M. Li, D. Dickson, H. Vlassara

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The apolipoprotein (apo) E-e4 altele is a strong genetic risk factor for both sporadic and familial cases of Alzheimer's disease (AD), however, the underlying molecular mechanism is still unknown. AGEs are irreversible glucose-protein or -lipid adducts that accumulate within tissues during normal aging. We have recently reported that amyloid plaques from AD brains contain high levels of AGEs and that AGE-amyloid peptide accelerates the formation of amyloid aggregates in vitro. Immunohistochemical studies of AD brain sections revealed strong AGE-immunoreactivity which was most intense within dense reticular amyloid deposits and extracellular neurofibrillary tangles (NFT) and less intense in intracellular NFT. Double staining, using anti-AGE and antiapoE antibodies, demonstrated that AGEs co-localized to a very high degree with apoE. To explore the possible biochemical association between apoE and AGE-modified proteins, we examined the binding of human apoE to in vitroprepared and radio-labeled AGE-bovine serum albumin (AGE-8SA), using Western ligand blot analysis. Recombinant human apoE exhibited AGE-specific binding activity in presence of excess unlabeled native BSA, with the dimeric form binding better than the monomeric form. Other apolipoproteins including apo A1, B, CI and CM, or serum pymicroblobulin, did not bind the AGE-BSA ligand. Judged by quantitation of radio-ligand blots, apoE-4 exhibited significantly greater (3 fold), AGE-binding activity than the apoE-3 isotype. In summary, our results suggest that apoE may participate in aggregate formation in the AD brain by binding to AGE-modified plaque components. The possibility that enhanced binding of apoE-4 to AGE-modified amyloid components might have pathogenic consequences in AD should be further explored.

Original languageEnglish (US)
Pages (from-to)A677
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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