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

Mech Ageing Dev. 2007 Jan;128(1):76-82. doi: 10.1016/j.mad.2006.11.014. Epub 2006 Nov 20.

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 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.

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Female
  • Folic Acid / blood
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Vitamin B 12 / blood

Substances

  • Folic Acid
  • Vitamin B 12