Susceptibility groups for Alzheimer's disease (OPTIMA cohort): Integration of gene variants and biochemical factors

Abstract

Information on gene variants and blood levels (APOE, BCHE-K, TF-C2, HFE-D, HFE-Y, ACE I/D, AR1; homocysteine, folate and vitamin B12) is available for participants in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort (n = 575). This information identified four risk sets for Alzheimer's disease (AD) using grade of membership analysis (GoM). Graded membership scores that relate individuals to each set are automatically generated. Sets I and III had low intrinsic risk. Set II had high intrinsic risk associated with multiple gene variants, e.g., APOE 44/34. Set IV also had high intrinsic risk demonstrating low folate and B12 levels. Membership in the high intrinsic risk sets was summed, coded as either close versus not close (≥0.80 versus <0.80) and input into logistic models to predict relative risk: close resemblance multiplied risk 80-fold for possible AD before age 65 and 55-fold for probable or definite AD at ages 65-74. These findings implicate both biochemical and genetic factors in the risk for AD and further support dietary supplementation with folate and vitamin B12 as a potential means to delay the onset of AD and/or its rate of progression. © 2006 Elsevier Ireland Ltd. All rights reserved.

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