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PMID:8089103

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Citation

LaDu, MJ, Falduto, MT, Manelli, AM, Reardon, CA, Getz, GS and Frail, DE (1994) Isoform-specific binding of apolipoprotein E to beta-amyloid. J. Biol. Chem. 269:23403-6

Abstract

Apolipoprotein E (apoE), particularly the e4 allele, is genetically linked to the incidence of Alzheimer's disease. ApoE is present in the extracellular senile plaques and intracellular neurofibrillary tangles associated with Alzheimer's disease. In vitro, apoE has been shown to bind beta-amyloid (A beta), an amyloidogenic proteolytic product of amyloid precursor protein. To analyze the interaction of A beta and apoE, we used Western immunoblotting of human A beta-(1-40)-peptide incubated with conditioned medium from HEK-293 cells transfected with either human apoE3 or apoE4 (products of the e3 and e4 alleles, respectively) cDNA. Nonreducing SDS-polyacrylamide gel electrophoresis revealed the presence of an approximately 45-kDa complex with both A beta and apoE immunoreactivity. The level of the apoE3.A beta complex was approximately 20-fold greater than that of the apoE4.A beta complex. This apoE isoform-specific binding pattern was maintained from pH 5.0 to 9.0, from 2 min to 24 h of peptide incubation, and at concentrations of apoE from 5 to 100 micrograms/ml and of A beta from 10 microM to 1 mM. The higher level of apoE3 binding to A beta is in contrast to previously published data using purified apoE (Strittmatter, W. J., Weisgraber, K.H., Huang, D. Y., Dong, L.-M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., and Roses, A.D. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 8098-8102). Factors responsible for the isoform-specific interactions between apoE and A beta will require further study before the apparent discrepancy between these data can be reconciled.

Links

PubMed

Keywords

Amyloid beta-Peptides/metabolism; Apolipoproteins E/metabolism; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Protein Binding; Recombinant Proteins; Time Factors

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:APOE

located_in

GO:0005576: extracellular region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:APOE

enables

GO:0001540: amyloid-beta binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(CHEBI:64646)

Seeded From UniProt

complete

HUMAN:APOE

enables

GO:0001540: amyloid-beta binding

ECO:0000314: direct assay evidence used in manual assertion

F

has_input:(CHEBI:64646)

Seeded From UniProt

complete

HUMAN:APOE

enables

GO:0042803: protein homodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:APOE

part_of

GO:0005576: extracellular region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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