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A Reexamination of Its Association With APOE

Stavra N. Romas, MD; Vincent Santana, BA; Jennifer Williamson, MS; Alejandra Ciappa, BS; Joseph H. Lee, PhD; Haydee Z. Rondon, MD; Pedro Estevez, MD; Rafael Lantigua, MD; Martin Medrano, MD; Mayobanex Torres, MD; Yaakov Stern, PhD; Benjamin Tycko, MD, PhD; Richard Mayeux, MD, MSc

Arch Neurol. 2002;59:87-91.

Objectives  To reexamine the association between the apolipoprotein E 4 allele (APOE 4) and familial Alzheimer disease (AD), and to search for novel genes that may be associated with susceptibility in Caribbean Hispanic families with a history of AD.

Methods  Families were identified in Caribbean Hispanic communities in the greater New York City area, the Dominican Republic, and Puerto Rico. Each family in the study cohort included at least 2 living relatives with a history of dementia. All family members underwent neuropsychological testing and medical and neurological examinations to establish the presence or absence of dementia and to specify the type of dementia.

Results  Over a 2-year period, 203 families were identified. Of these, 19 families had at least 1 family member with onset of dementia before age 55 years, with 8 of the 19 families showing an association with a previously unreported presenilin mutation. Multiple cases of AD were identified in 29 families. Overall, there were 236 affected sibling pairs with AD available for analysis. The average age at onset was 74 years. The presence of APOE 4 was strongly associated with AD.

Conclusions  Both early-onset and late-onset familial AD occur in Caribbean Hispanics. In contrast to sporadic AD, late-onset familial AD among Caribbean Hispanics is strongly associated with APOE 4. Future attempts to identify additional susceptibility genes should consider the effects of APOE 4.

From the Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Drs Romas, Rondon, Estevez, Lantigua, Stern, and Mayeux, Mr Santana, and Ms Williamson), the Gertrude H. Sergievsky Center (Drs Romas, Lee, Rondon, Estevez, Lantigua, Stern, and Mayeux, Mr Santana, and Ms Williamson), the Departments of Medicine (Dr Lantigua), Neurology (Drs Romas and Mayeux), Pathology (Dr Tycko and Ms Ciappa), and Psychiatry (Dr Mayeux), College of Physicians and Surgeons, and the Division of Epidemiology, Mailman School of Public Health (Drs Lee and Mayeux), Columbia University, New York, NY; the Universidad Tecnologica de Santiago, Santiago (Dr Medrano), and the Plaza de la Salud, Santo Domingo (Dr Torres), Dominican Republic.

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