The average lifetime risk of developing AD is estimated to be between 10 and 12% (until the age of 75–80 years).3–5 The ε4 variant of the APOE gene is associated with an increased risk of late-onset AD,5,6 but this risk is confounded by other factors. These factors include those that cannot be modified (eg other genetic variants, gender, family history, possibly ethnicity) and modifiable risk factors (eg diet, exercise, cardiovascular health, environment). The clinical utility of knowing ε4 status is uncertain.3,5–7
Research suggests that heterozygous carriers of the ε4 variant have an approximately threefold increase in risk of developing AD, while homozygous carriers have an approximately 15-fold increase in risk. Having a first-degree relative with AD doubles the risk of developing the disease.3,7,8
The ε4 variant is neither necessary nor sufficient to cause AD, and risk estimates are problematic given the range of confounding factors. Therefore, the clinical utility of genetic testing is uncertain.2,3