Individuals with Down syndrome (DS) experience increased risk of Alzheimer's disease (AD). Recent studies suggest that a vaccine against AD may be forthcoming. Parental buy-in is critical to the success of any intervention in this population, as adults with DS often rely on familial support. This study aims to characterize parents' perceptions of a hypothetical vaccine to prevent AD in individuals with DS. A mixed-methods, anonymous survey was distributed via social media. Participants were asked about their experiences with DS and reactions to proposed interventions. Open-ended responses were thematically analyzed using NVivo 12. Of 1,093 surveys initiated, 532 were completed. Of the parents sampled (N = 532), a small majority (54.3%), supported the proposed AD vaccine. All expressed the need for extensive pre-enrollment education and minimal risk. For many, limited research and long-term sequelae were concerns.