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

Warren J. Strittmatter, Ann M. Saunders, Donald Schmechel, Margaret Pericak-Vance, Jan Enghild, Guy S. Salvesen, Allen D. Roses

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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 βA4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the βA4 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-ε4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-εA in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 ± 0.06; the allele frequency of APOE-ε4 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 (US)
Pages (from-to)1977-1981
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Mar 1 1993
Externally publishedYes


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