GENETIC-FACTORS FOR THE DEVELOPMENT OF ALZHEIMER-DISEASE IN THE CHEROKEE INDIAN

Objective: To study the relationship between the genetic degree of Che rokee ancestry, the apolipoprotein E E4 (APOE*E4) allele type, and th e development of Alzheimer disease (AD) in individuals from the Cherok ee Nation who reside in northeastern Oklahoma. Setting: Alzheimer dise ase center satellite clinic and university departments of neurology, p sychiatry, and academic computing. Design: Standardized dementia evalu ations based on criteria from the National Institute of Neurological a nd Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 ye ars or older to establish a diagnosis of AD. Twenty-six control subjec ts were recruited and similarly assessed. The APOE allele type determi nations were obtained on all patients and control subjects. Appropriat e statistical analyses were used to compare the genetic degree of Cher okee ancestry, the APOE allele type, and the development of AD. Result s: The data indicated that as the genetic degree of Cherokee Indian an cestry increased, the representation of AD decreased. The 9 patients w ith AD with a greater than 50% genetic degree of Cherokee ancestry con stituted 35% of the group with AD. The 17 remaining patients with AD w ho were less than 50% Cherokee constituted 65% of the group with AD. I n contrast, 17 (65%) of the control subjects were more than 50% Cherok ee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APO EE4 allele status, diminished with increasing age, suggesting an age- related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 ye ars. Conclusions: A greater genetic degree of Cherokee ancestry reduce s the risk of developing AD and, thus, seems protective. This protecti ve genetic factor is independent of APOE allele type and diminishes wi th age.