Sixty participants underwent whole genome sequencing and APOE genotyping. PRS for AD and coronary artery disease (CAD) were generated using Allelica DISCOVER and PREDICT v3.1.6 platforms, excluding APOE for AD. Results were adjusted to ancestry-specific thresholds and reported as average v.s. high risk (≥ 2X relative risk). One year after learning their APOE and other genetic test results, participants received disclosure only on their PRS results, delivered through structured counseling. Post-disclosure surveys assessed participants' understanding, emotional responses, perceived utility, and preferences regarding genetic risk information.

We disclosed AD and CAD PRS to 60 adults (29 cognitively normal; 21 mild cognitive impairment; 7 AD dementia; 3 other dementia). Ten (17%) and 21 (35%) had high/elevated AD and CAD risks, respectively. Interestingly, nearly all participants with high AD PRS did not carry an APOE ε4 allele (n = 9, 90%), underscoring added value beyond traditional risk markers. Most participants reported understanding their PRS (95%), found it useful for planning (90%), and 83% endorsed broader PRS use in AD risk assessment. Emotional responses were largely positive (93%), with participants feeling prepared and glad to receive results, though 7% desired more preparation. Disclosure was feasible across cognitive groups without major adverse reactions.

Our study provides early evidence that PRS disclosure in AD is feasible and well-received, supporting its integration into precision medicine practice. PRS adds predictive information beyond APOE and enhances risk communication and patient engagement. Larger-scale studies will be needed to confirm these findings and refine best practices.