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

W J Strittmatter, A M Saunders, D Schmechel, M Pericak-Vance, J Enghild, G S Salvesen, A D Roses

    Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

    Abstract

    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
    Volume90
    Issue5
    Pages (from-to)1977-81
    Number of pages4
    ISSN0027-8424
    Publication statusPublished - 1993

    Keywords

    • 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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