Background: Participants willing to provide genetic samples are needed to propel research on Alzheimer’s disease (AD) treatment and prevention forward. A limited public understanding of what AD genetic research entails and concerns about participation may constitute recruitment challenges. Objectives: This study seeks to understand how well older adults understand AD genetic research and whether their understanding is related to concerns about participation or willingness to engage. Methods: Our surveys included a mock consent form with corresponding knowledge and opinion questions regarding AD. The surveys were mailed to participants from the University of Kentucky Alzheimer’s Disease Center and to a list of randomly selected individuals within the same age range from a local voter registration list. Descriptive and multivariable linear regression analyses were conducted. Results: The returned surveys (n = 502) demonstrated limits to what the respondents understood immediately after reading the relevant material, with a mean summary knowledge score of 74.5 out of 100. While comprehension gaps were not related to level of concern or willingness to engage, concerns were related to willingness to engage. Concerns were greater among individuals not actively involved in research, individuals from minority groups, and those with higher levels of education. Conclusions: Focusing on concerns specifically, rather than on knowledge more generally, may help increase participation.