Dose‐dependent association of apolipoprotein e allele ε4 with late‐onset, sporadic Alzheimer's disease

We examined the apolipoprotein E (apo E) genotypes in 47 patients with late‐onset sporadic Alzheimer's disease (mean age at onset ± standard deviation, 72.2 ± 6.4 years), 8 with late‐onset familial Alzheimer's disease (75.5 ± 5.1 years), 18 with early‐onset sporadic Alzheimer's disease (52.8 ± 4.7 years), and 10 with early‐onset familial Alzhemer's disease (52.0 ± 6.8 years) in Japan and compared them with genotypes in control subjects. In late‐onset sporadic Alzheimer's disease, apo E‐ε4 frequency increased significantly (ε4 frequency: 0.34 vs 0.095 in controls, p < 0.0001), and the odds ratio, which represents the strength of association between Alzheimer's disease and apo E‐ε4 gene (3 [95% confidence interval, 2–6] in one dose; 43 [95% confidence interval, 12–154] in two doses). This study also suggested that apo E‐ε4 is associated with both late‐onset (ε4: 0.31) and early‐onset familial Alzheimer's disease (ε4: 0.35). In contrast, we found no association between apo E‐ε4 and early‐onset sporadic Alzheimer's disease (ε4: 0.08). These results indicate that the risk of developing late‐onset sporadic Alzheimer's disease is markedly dependent on the dose of apo E‐ε4, while apo E‐ε4 does not appear to be a major risk factor for early‐onset sporadic Alzheimer's disease.