The identification of healthy individuals harboring amyloid pathology constitutes one important challenge for secondary prevention clinical trials in Alzheimer’s disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60% unnecessary CSF/PET tests and to reduce 47% of the cost of recruitment when used in a simulated clinical trial setting. This recruitment strategy capitalizes on already acquired MRIs to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for AD screening. This protocol could foster the development of secondary prevention strategies for AD.