THE ALZHEIMER’S PREVENTION INITIATIVE (API) PROGRAM: GENETIC TESTING AND DISCLOSURE STRATEGIES

The Alzheimer's Prevention Initiative (API) is a collaborative funded by the NIH, philanthropy, and industry to conduct preclinical Alzheimer's disease (AD) trials in people who, based on age and genetics, are at elevated risk of developing AD symptoms. The API's Generation Study is enrolling apolipoprotein E (APOE) e4 homozygotes age 60-75. To support this and future trials, API established an interdisciplinary APOE Genetic Testing and Disclosure Committee whose aims include establishing an APOE genetic testing program to enrich referrals to studies, known as GeneMatch; updating APOE risk estimates; and evaluating disclosure of genetic risk and its impact. GeneMatch is a trial-independent program performing APOE genotyping in individuals age 55-75 to enrich referrals to prevention studies. GeneMatch uses buccal swab kits sent via mail and does not disclose APOE results to participants, either directly or inadvertently through referral to studies. Recruiting studies, however, may ask or invite individuals to learn their APOE results. The Generation Study includes standardized disclosure of AD risk by APOE genotype and the assessment of the psychological effects of genetic disclosure. A separate, investigator-initiated ancillary study, CONNECT 4 APOE, is examining the feasibility and efficacy of remote delivery (phone vs. real-time videoconferencing) methods for disclosing APOE results. Other investigator-initiated, ancillary studies examine the impact of APOE disclosure on objective and subjective cognitive functioning (“stereotype threat”), and its effect on families. GeneMatch launched in 2015 and aims to enroll tens of thousands of participants. The Generation Study launched in November 2015; enrollment and genetic disclosure are ongoing. The CONNECT 4 APOE, Stereotype Threat, and Impact on Families ancillary studies will launch in 2016. Results from these efforts will be presented. GeneMatch is a key element of the API, facilitating enrollment into a range of research studies, including the Generation Study. Results from Generation Study's disclosure program and ancillary studies will help determine the effects of APOE disclosure across different modes of delivery and enhance appreciation of the psychosocial implications of high-risk results, with lessons for clinical practice and precision medicine, as well as future trials in genetically enriched populations.