THE GENETIC factors that predispose individuals to Alzheimer disease (AD) have not yet been fully defined. The proportion of AD that has a major gene component has been estimated to be at least 36%.
1 Alzheimer disease associated with mutations in the amyloid precursor protein,
2 presenilin 1,
3 and presenilin 2
4,5 genes is transmitted as an autosomal dominant and highly penetrant trait, but, collectively, these defects account for less than 2% of all AD cases.
6 Although the apolipoprotein E gene (
APOE) ϵ4 allele accounts for an estimated 45% to 60% of the genetic risk for AD,
7,8 the observation that ϵ4 is neither necessary nor sufficient to cause the disease
8 has prompted the investigation of other candidate susceptibility genes.