Now is the time: the need to update guidance to expand access to APOE genetic testing

Interest in APOE testing has increased due to an aging population, direct-to-consumer testing options, media coverage and FDA approval of anti-amyloid therapies. Previous Alzheimer’s disease (AD) guidelines cautioned against APOE testing in asymptomatic individuals. However, updated guidance is warranted due to the changing landscape and research demonstrating low adverse psychological outcomes of APOE testing. With testing for APOE now recommended prior to anti-amyloid therapies, more symptomatic individuals will be identified as having the higher risk ε4 variant. The children and siblings of the symptomatic individuals who test positive will have at least a 50% risk of also having an ε4 and may subsequently seek testing. Since testing for APOE is generally not clinically available to asymptomatic individuals, they may pursue direct-to-consumer genetic testing and, therefore, be tested without a clinician’s involvement or counseling. Given limitations and caveats of APOE testing, it is important that patients have access to education, counseling and testing in labs certified for clinical testing. Pre- and post-test education and counseling content for APOE testing, including risk figures, are provided in this Perspective. Both Alzheimer’s disease and cardiovascular disease risks associated with APOE should be addressed for all individuals undergoing testing. Given that it has been over a decade since APOE guidance was issued, the time has come for the medical community to discuss the changing landscape, expand APOE genetic testing access to individuals at higher risk, and update guidelines.