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.
Li
Y J
YJ
Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA. yiju.li@duke.edu
Hauser
M A
MA
Scott
W K
WK
Martin
E R
ER
Booze
M W
MW
Qin
X J
XJ
Walter
J W
JW
Nance
M A
MA
Hubble
J P
JP
Koller
W C
WC
Pahwa
R
R
Stern
M B
MB
Hiner
B C
BC
Jankovic
J
J
Goetz
C G
CG
Small
G W
GW
Mastaglia
F
F
Haines
J L
JL
Pericak-Vance
M A
MA
Vance
J M
JM
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001315:Australia / Q000453:epidemiology; D003071:Cognition; D003704:Dementia / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D010375:Pedigree; D012306:Risk; D014481:United States / Q000453:epidemiology
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E