Article

Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer's disease population

Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse VA Medical Center, Syracuse, New York 13210, USA.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.27). 09/2008; 147B(6):822-9. DOI: 10.1002/ajmg.b.30694
Source: PubMed

ABSTRACT 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.

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    • "The distinct difference in hippocampal insulin responses across apolipoprotein E-epsilon-4 genotype in AD suggests that these two sub-populations might exhibit fundamental differences in brain insulin sensitivity in AD. It is interesting to note that apolipoprotein E-epsilon-4 negative AD are at increased risk for type 2 diabetes and overweight, (Profenno & Faraone, 2008) providing evidence of peripheral insulin signaling disparities across apolipoprotein E-epsilon-4 genotype. Although the biochemical reasons for this genetic-based difference in insulin brain responses cannot be determined from our study, apolipoprotein E- epsilon-4 genotype in AD nevertheless appears to be an important consideration when assessing insulin effects on both memory and brain activity in AD, and might be an important factor if insulin-based AD treatment is considered in the future. "
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    Biochimica et Biophysica Acta 09/2008; 1792(5):454-69. DOI:10.1016/j.bbadis.2008.08.005 · 4.66 Impact Factor
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