Apolipoprotein E polymorphism and age of onset for Alzheimer's disease in a bi-ethnic sample.
OBJECTIVE
This study examined the association between the Apolipoprotein-E epsilon4 allele (APOE epsilon4) and age of disease onset in a bi-ethnic sample of community dwelling Alzheimer's disease (AD) patients.


METHODS
Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic.


METHODS
A clinic-based cohort of white non-Hispanic (WNH; n=601) and white Hispanic (WH; n = 359) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria.


METHODS
Global cognitive functioning of the subjects was evaluated using the Mini-mental State Exam. The age of onset of AD was calculated from the patient's current age minus the reported duration of disease obtained from a knowledgeable family member.


RESULTS
A significant relationship was discovered between APOE epsilon4 and age of onset for WNH, with lower ages of onset among patients carrying the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes in relation to patients with the epsilon3/epsilon3 genotype. The results revealed a more modest effect for APOE genotype in the WH cohort, with a lower age of onset witnessed among epsilon4 positive patients (epsilon2/epsilon4, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes) in comparison to epsilon4 negative patients (epsilon2/epsilon2, epsilon2/epsilon3 and epsilon3/epsilon3 genotypes).


CONCLUSIONS
The association between the epsilon4 allele and earlier age of onset was more pronounced in WNH compared to WH patients, suggesting the impact of APOE polymorphism on clinical phenotype may be different for distinct ethnic groups in the U.S.
Harwood
Dylan G
DG
Neuropsychiatric Institute and Hospital, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, USA.
Barker
Warren W
WW
Ownby
Raymond L
RL
St George-Hyslop
Peter
P
Mullan
Michael
M
Duara
Ranjan
R
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D003430:Cross-Sectional Studies; D005006:Ethnicity / Q000523:psychology* / Q000706:statistics & numerical data*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*
D001057:Apolipoproteins E