The apolipoprotein E ε4 allele selectively increases the risk of frontotemporal lobar degeneration in males

Objective: To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent. Methods: The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE epsilon 4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the some geographical region. Analyses were done according to clinical subtype or sex. Results: The APOE epsilon 4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole control group (14.1%), while the APOE epsilon 2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE epsilon 4 allele frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE epsilon 2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE epsilon 2 nor APOE epsilon 4 allele frequency varied significantly between any of the clinical subtypes. Conclusions: In FTLD not associated with mutations in tau gene, possession of APOE epsilon 4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women.