Familial Alzheimer disease in Latinos: interaction between APOE, stroke, and estrogen replacement.
BACKGROUND
Factors that modify risk related to APOE variants have been examined primarily in unrelated patients and controls, but seldom in family-based studies. Stroke, vascular risk factors, estrogen replacement therapy (ERT), head injury (HI), and smoking have been reported to influence risk of sporadic but not familial Alzheimer disease (AD).


OBJECTIVE
To examine the potential relationship between these risk factors and APOE, the authors used a family study design in a population in which the APOE-epsilon4 variant is strongly associated with risk of AD.


METHODS
Latino families primarily from the Caribbean Islands in which two or more living relatives had dementia were identified in the New York City metropolitan area, the Dominican Republic, and Puerto Rico. A total of 1,498 participants from 350 families underwent a clinical interview, medical and neurologic examinations, neuropsychological testing, and APOE genotyping. Diagnosis was made by consensus using research criteria for AD.


RESULTS
APOE-epsilon4 was associated with a nearly twofold increased risk of AD. A history of stroke was also associated with a fourfold increased risk. A statistical interaction between APOE-epsilon4 and stroke was observed. Women with an APOE-epsilon4 who took ERT did not have an increased risk of AD, but in women with a history of stroke ERT was a deleterious effect modifier.


CONCLUSIONS
APOE-epsilon4 and stroke independently increase risk of familial Alzheimer disease (AD) among Latinos, and may interact to further increase AD risk. Among women, the risk of AD associated with APOE-epsilon4 may be attenuated by a history of ERT.
Rippon
G A
GA
Department of Neurology, Gertrude H. Sergievsky Center, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Tang
M X
MX
Lee
J H
JH
Lantigua
R
R
Medrano
M
M
Mayeux
R
R
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D015984:Causality; D004293:Dominican Republic / Q000453:epidemiology; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data; D004967:Estrogens / Q000627:therapeutic use; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D011647:Puerto Rico / Q000453:epidemiology; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004967:Estrogens