1993/03/01 by Warren J. Strittmatter, Ann M. Saunders, D. E. Schmechel +4 · 18 citations
Medicine · #Alzheimer's disease research and treatments #Cholinesterase and Neurodegenerative Diseases #Dementia and Cognitive Impairment Research #Apolipoprotein E #Alzheimer's disease #Senile plaques #Apolipoprotein B #Allele #Pathogenesis #Degenerative disease #Biology #Internal medicine #Endocrinology #Medicine #Genetics #Disease #Gene #Cholesterol
paper · pdf · doi:10.1073/pnas.90.5.1977
openalex publication_date 1993/03/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
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.