Parkinson's disease and apolipoprotein E: possible association with dementia but not age at onset.
Idiopathic Parkinson's disease (PD) is an age-dependent, neurodegenerative condition frequently associated with dementia. Although it is predominantly a sporadic disease, 20-30% of cases are familial, suggesting a complex mode of inheritance. Apolipoprotein E (APOE) allele epsilon4 has been associated with familial and sporadic late-onset senile dementia of the Alzheimer's type. To investigate the role of this gene in the development of dementia associated with PD and age at onset of PD, we evaluated the frequency of APOE gene polymorphism in a sample of PD patients with (n=118) and without (n=167) a family history, as well as matched normal controls (n=96). The PD sample was categorized according to age at onset and presence or absence of dementia. Kaplan-Meier survival analysis was used to plot genotype-specific age at onset distribution curves. Allele frequencies of APOE in PD patients with and without a family history and normal controls were not significantly different. APOE genotypes were also similar between the groups. However, the frequencies of epsilon4 allele and epsilon4/- genotype in the PD group with dementia were more than twofold higher than in normal controls, and the differences were statistically significant. There were no differences in the allele and genotype frequencies of the APOE gene between PD groups with different age at onset. The familial PD had significantly earlier age at onset than sporadic PD (Log-rank test, P=0.027). The age at onset distribution curves for different genotype groups were similar, and their differences were not statistically significant (P=0.38). After the Bonferroni's correction for multiple tests, the positive results are not significant at the P<0.05 level. We conclude that APOE does not play an important role in susceptibility to PD or age at onset of PD, but may play a role in dementia associated with PD in our sample.
Parsian
Abbas
A
University of Louisville Birth Defects Center, University of Louisville Health Sciences Center, Louisville, Kentucky 40202, USA. parsian@louisville.edu
Racette
Brad
B
Goldsmith
L Jane
LJ
Perlmutter
Joel S
JS
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D003704:Dementia / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics; D016019:Survival Analysis
D001057:Apolipoproteins E