Several lines of evidence suggest that the variable age at onset of Parkinson disease (PD) is likely influenced by genes. The apolipoprotein E (APOE) gene is associated with onset of Alzheimer disease, and possibly other neurodegenerative disorders. APOE has been investigated in relation to onset of PD, but results have been inconsistent. The aim of the present study was to determine if APOE genotypes are associated with onset age of PD, using a patient population large enough to assure sufficient power. We studied 521 unrelated Caucasian patients with idiopathic PD from movement disorder clinics in Oregon and Washington. Genotyping and statistical analyses were carried out using standard methods. Age at onset of PD was significantly earlier in patients with the ε3ε4/ε4ε4 genotype than in patients with the ε3ε3 genotype (56.1 ± 10.9 vs. 59.6 ± 11.0, P = 0.003). The significantly earlier onset of PD was not influenced by the possible effects of recruitment site, family history and gender. The effect of the ε2ε3 genotype on onset of PD differed between the two recruitment sites. There was a trend for earlier onset of PD in ε2ε3 patients than in ε3ε3 patients only in the Oregon sample. In conclusion, APOE is associated with age at onset of PD. © 2001 Wiley-Liss, Inc.