Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia.
The epsilon4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD. It is possible that APOE4 may also play a role in the etiology of other neurodegenerative disorders, such as Parkinson's disease (PD). APOE genotype, age of onset, disease duration, smoking history, and dementia status were collected for families with PD, yielding 324 Caucasian families with complete information. Logistic regression employing one individual per family and including age of onset and disease duration as covariates demonstrated a significantly increased risk of dementia for those individuals having inherited at least one epsilon4 allele (OR=3.37; P=0.002). Survival analyses also demonstrated a significantly earlier age of onset for those subjects with at least one epsilon4 allele (59.7 years) as compared with those homozygous for the more common epsilon3 allele (62.4 years; P=0.009). Thus, consistent with previous studies, we find evidence that the presence of an epsilon4 allele results in significantly earlier onset of PD and a greater likelihood of dementia. It appears the similarities between PD and AD may be due to an overlap in the diseases' genetic etiology.
Pankratz
Nathan
N
Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, Indiana, USA.
Byder
Lisa
L
Halter
Cheryl
C
Rudolph
Alice
A
Shults
Clifford W
CW
Conneally
P Michael
PM
Foroud
Tatiana
T
Nichols
William C
WC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D020961:Lewy Body Disease / Q000235:genetics*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000235:genetics*; D012306:Risk; D013223:Statistics as Topic; D016019:Survival Analysis
D053327:Apolipoprotein E4; D001057:Apolipoproteins E