Susceptibility groups for Alzheimer's disease (OPTIMA cohort): integration of gene variants and biochemical factors.
Information on gene variants and blood levels (APOE, BCHE-K, TF-C2, HFE-D, HFE-Y, ACE I/D, AR1; homocysteine, folate and vitamin B(12)) 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., APOE44/34. Set IV also had high intrinsic risk demonstrating low folate and B(12) levels. Membership in the high intrinsic risk sets was summed, coded as either close versus not close (>or=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 B(12) as a potential means to delay the onset of AD and/or its rate of progression.
Corder
Elizabeth H
EH
Center for Demographic Studies, Duke University, Durham, NC 27708, USA. elizabethcorder@hotmail.com
Beaumont
Helen
H
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000097:blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D014805:Vitamin B 12 / Q000097:blood
D005492:Folic Acid; D014805:Vitamin B 12