Professor of Psychiatry and Behavioral Sciences and of Neuroscience and Physiology.
Diabetes and overweight associate with non-APOE4 genotype in an alzheimer's disease population†
Article first published online: 11 JAN 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 147B, Issue 6, pages 822–829, 5 September 2008
How to Cite
Profenno, L. A. and Faraone, S. V. (2008), Diabetes and overweight associate with non-APOE4 genotype in an alzheimer's disease population. Am. J. Med. Genet., 147B: 822–829. doi: 10.1002/ajmg.b.30694
Please cite this article as follows: Profenno LA, Faraone SV. 2008. Diabetes and Overweight Associate With Non-APOE4 Genotype in an Alzheimer's Disease Population. Am J Med Genet Part B 147B:822–829.
- Issue published online: 22 AUG 2008
- Article first published online: 11 JAN 2008
- Manuscript Accepted: 13 NOV 2007
- Manuscript Received: 24 MAY 2007
Type 2 diabetes is a risk factor for late-onset Alzheimer's disease (AD), and studies suggest that pathogenic effects of diabetes and insulin resistance may be associated with non-APOE4 AD. Therefore, we examined association of the APOE4 allele with diabetes in an AD population. Retrospective and cross-sectional clinical and APOE-genotype data on 465 cases with probable or definite AD previously ascertained by the National Institute of Mental Health Genetics Initiative were analyzed by regression analysis. Dependent variables included presence of APOE4 alleles and AD onset age. Diabetes was the independent variable and covariates included gender, hypertension, and other potentially confounding variables. We also examined for interactions involving weight status as overweight and obesity are independent risk factors for insulin resistance, diabetes and AD. Prevalence of diabetes was 13% among AD cases without an APOE4 allele and 5–6% among AD cases with one or two APOE4 alleles. Odds ratio for diabetes was 0.26 [95% CI: 0.09–0.73; P = 0.011] by APOE4 status after adjusting for all covariates. Diabetes did not associate with AD onset age. Among other independent variables included in the model, APOE4 and diuretic medication treatment were associated with AD onset age. In a subset of cases with body mass index determinations, overweight also exhibited an inverse association with APOE4 and associated with decreased non-APOE4 AD onset age. Pathogenic mechanisms associated with diabetes and overweight are enriched in AD cases without an APOE4 allele. © 2008 Wiley-Liss, Inc.