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 language | English |
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Journal | Proceedings of the National Academy of Sciences (PNAS) |
Volume | 90 |
Issue | 5 |
Pages (from-to) | 1977-81 |
Number of pages | 4 |
ISSN | 0027-8424 |
Publication status | Published - 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