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Several studies have reported an association of the apolipoprotein E allele epsilon 4 (APOE*4) to familial and sporadic late-onset Alzheimer's disease (LOAD). Here we report on the relationship between APOE*4 and early-onset Alzheimer's disease (EOAD) in a Dutch population-based study. The frequency of the APOE*4 allele was 2.3 times higher among EOAD cases compared to controls. Among patients, the allele frequency was 1.6 times higher in those with a positive family history than in those without. A significant increase in risk of EOAD was found for subjects homozygous for APOE*4 regardless of family history of dementia, but an increase in EOAD risk for APOE*4 heterozygotes could only be shown in subjects with a positive family history. Our study demonstrates a significant association between APOE*4 and EOAD which is modified by family history of dementia.

Original publication




Journal article


Nature genetics

Publication Date





74 - 78


Department of Epidemiology & Biostatistics, Erasmus University, Medical School, Rotterdam, The Netherlands.


Humans, Alzheimer Disease, Apolipoproteins E, Odds Ratio, Risk Factors, Polymerase Chain Reaction, Age of Onset, Gene Frequency, Genotype, Genes, Dominant, Alleles, Adult, Aged, Middle Aged, Family Health, Netherlands, Female, Male, Apolipoprotein E4