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Apolipoprotein E  4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics
Lucia Olarte, BS;
Nicole Schupf, PhD;
Joseph H. Lee, DPH;
Ming-Xin Tang, PhD;
Vincent Santana, MBA;
Jennifer Williamson, MS;
Prashanthi Maramreddy, PhD;
Benjamin Tycko, MD, PhD;
Richard Mayeux, MD, MSc
Arch Neurol. 2006;63:1586-1590.
Background The primary effect of the apolipoprotein E  4 (APOE 4) allele is on the age at onset of Alzheimer disease (AD).
Objective To investigate whether the presence of the APOE 4 allele can account for the earlier age at onset of familial AD (FAD) compared with sporadic AD (SAD).
Design Population-based, case series ascertained in a prospective study of aging and dementia in Medicare recipients aged 65 years or older.
Setting Clinics in northern Manhattan and in the Dominican Republic and Puerto Rico.
Participants There were 680 Caribbean Hispanic subjects: 111 patients with FAD, with at least 1 family member with dementia; 163 patients with SAD; and 406 elderly persons without dementia or other illnesses.
Main Outcome Measure Age at onset of dementia was examined in relation to frequency of APOE 4. Sex, education, and medical risk factors for stroke, hypertension, diabetes, and heart disease were examined as effect modifiers.
Results The mean age at onset of AD was significantly lower in FAD than in SAD, and a statistically significant dose effect of the APOE 4 allele was present for age at onset in FAD (P = .001) but not in SAD. The age at onset in patients homozygous for the APOE 4 allele with FAD and SAD was similar. Compared with SAD, the major difference was younger age at onset in patients with FAD who were heterozygous for the APOE 4 allele and those without an APOE 4 allele.
Conclusions Apolipoprotein E 4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD. This suggests that among individuals with a family history of AD and the APOE 4 allele, additional genetic or environmental factors may accelerate the onset of dementia.
Author Affiliations: Gertrude H. Sergievsky Center (Ms Olarte and Drs Schupf, Lee, Tang, Williamson, Tycko, Maramreddy, and Mayeux, and Mr Santana), Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Ms Olarte and Drs Schupf, Lee, Williamson, Tycko, Maramreddy, and Mayeux, and Mr Santana), Departments of Neurology (Drs Tycko and Mayeux), Psychiatry (Dr Mayeux), and Pathology (Drs Schupf, Lee, and Mayeux), and Departments of Epidemiology (Drs Schupf, Lee, and Mayeux) and Biostatistics of the Mailman School of Public Health, Columbia University College of Physicians and Surgeons, New York, NY; Laboratory of Epidemiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island (Drs Schupf and Tang).
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