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 A Pericak-Vance, Jan Enghild, Guy S. Salvesen, Allen D. Roses

Research output: Contribution to journalArticle

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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 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
Pages (from-to)1977-1981
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number5
StatePublished - Mar 1 1993
Externally publishedYes

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Apolipoproteins E
Amyloid
Gene Frequency
Apolipoprotein E4
Alzheimer Disease
Alleles
Amyloid Plaques
Peptides
Neurofibrillary Tangles
Blood Vessels
Cerebrospinal Fluid
Protein Isoforms
Chromosomes
Alzheimer disease type 2
Amino Acids
Genes

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Apolipoprotein E : High-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. / Strittmatter, Warren J.; Saunders, Ann M.; Schmechel, Donald; Pericak-Vance, Margaret A; Enghild, Jan; Salvesen, Guy S.; Roses, Allen D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 5, 01.03.1993, p. 1977-1981.

Research output: Contribution to journalArticle

Strittmatter, Warren J. ; Saunders, Ann M. ; Schmechel, Donald ; Pericak-Vance, Margaret A ; Enghild, Jan ; Salvesen, Guy S. ; Roses, Allen D. / Apolipoprotein E : High-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 5. pp. 1977-1981.
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