The population analyzed in this study notably contains some very old individuals, allowing the authors to carefully study the lifetime influence of ApoE4 on Alzheimer’s disease. They find that, in general, Alzheimer’s disease is best described by a model where a fraction of the population is resistant to the disease and will never develop it no longer how long they live. In this model, 25-30% of individuals appear to be in this “resistant” group.
When individuals are segregated according to ApoE4 carrier status (homozygous, heterozygous, and non-carrier), they find that the age of onset is shifted earlier for carriers of ApoE4 (Figure 3). For non-carriers, ~50% are diagnosed with Alzheimer’s disease by the age of ~95 years. This shifts to ~91 years of age for individuals heterozygous for ApoE4 (~4 years earlier onset) and ~82 years for ApoE4 homozygotes (~13 years earlier onset).
Investigating the incidence of Alzheimer’s by age 80 in their model, 7% of all individuals on average have developed it by this age (Figure 2). Non-carriers have an average rate of ~5%, heterozygotes a rate of ~10% (2x), and homozygotes a rate of ~40% (8x) (from Figure 3). Penetrance in GET-Evidence is evaluated according to these numbers, with 3% increased attributable risk for heterozygotes (from 7%) and 33% increased attributable risk for homozygotes.