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

Topic: Amyloid, tau and blood-test diagnosis

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.

Key findings

• 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.

Why it matters

In 30 people with late-onset Alzheimer's disease, each from a different affected family, half of their APOE gene copies were the type 4 form (allele frequency 0.50), compared with 0.16 in 91 age-matched unrelated controls (P = 0.014). In separate laboratory tests, apolipoprotein E in spinal fluid bound tightly to synthetic beta-amyloid, the main component of Alzheimer's plaques, and the protein was found in plaques and tangles. The authors only "suggested" a role for the E4 form in familial late-onset disease: this small study measured how common the allele was, not any individual's risk, and it tested no treatment.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.90.5.1977
• PubMed: 8446617
• Original source →
• Free full text: PubMed Central →

Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).

@article{strittmatter1993-8446617,
  author  = {Strittmatter, W. J. and Saunders, A. M. and Schmechel, D. and Pericak-Vance, M. and Enghild, J. and Salvesen, G. S. and Roses, A. D.},
  title   = {{Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1993},
  doi     = {10.1073/pnas.90.5.1977},
  pmid    = {8446617},
  url     = {https://doi.org/10.1073/pnas.90.5.1977}
}

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