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Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease

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  • W J Strittmatter, Denmark
  • A M Saunders, Denmark
  • D Schmechel, Denmark
  • M Pericak-Vance, Denmark
  • J Enghild
  • G S Salvesen, Denmark
  • A D Roses, Denmark
  • Interdisciplinary Nanoscience Center
  • Department of Molecular Biology
Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.
Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Pages (from-to)1977-81
Number of pages4
Publication statusPublished - 1993

    Research areas

  • Alleles, Alzheimer Disease, Amino Acid Sequence, Amyloid beta-Protein, Animals, Apolipoproteins E, Brain, Gene Frequency, Humans, Lemur, Molecular Sequence Data, Peptides, Protein Binding, Solubility

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