Apolipoprotein E controls the risk and age at onset of Parkinson disease

Background: Similarities between Alzheimer disease ( AD) and Parkinson disease (PD) suggest a possible role for apolipoprotein E ( APOE) in PD. Most previous studies seeking to establish such a link used case-control datasets and results have been inconsistent. Objective: To investigate APOE's role in PD using family-based association analyses. Methods: APOE functional polymorphisms were genotyped for 658 PD affected families, including 282 multiplex and 376 singleton families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the effect of APOE on age at onset of PD. Results: APOE was significantly associated with risk of developing PD. Stratified analysis revealed that APOE was most strongly associated with families with a positive PD family history (global p = 0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a negative association of APOE-4 (p = 0.015) with age at onset in PD. Conclusions: The APOE-4 allele increases risk and decreases age at onset of PD, an association that may not be dependent upon cognitive impairment.