Project Summary Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by pathological processes that occur many years before clinical symptoms manifest. One of the hallmark features of AD is the accumulation of beta-amyloid (Aβ) plaques in the brain. Detecting and quantifying Aβ burden is crucial for identifying individuals at high risk of AD progression and evaluating the effectiveness of potential treatments. Currently, the primary method for assessing Aβ burden is using radioactive positron emission tomography (PET) tracers. However, PET imaging has several limitations, including high costs, limited spatial resolution, and constraints on frequent measurements, which are essential for tracking changes over time and evaluating treatment outcomes. In response to these limitations, this project sets out to develop and optimize an innovative magnetic resonance imaging (MRI) technique that is sensitive to pathological aggregates such as Aβ, with the goal of supplementing the traditional amyloid PET. Under aim 1, the novel 3D MRI sequence will be implemented and optimized for Aβ detection in the brain; Under aim 2, the signal generated from the saturation transfer MRI will be compared to the uptake values of the amyloid PET for the whole brain and in key brain regions. Ultimately, our goal is to deliver a clinically useful MRI method for Aβ detection. This method has the potential to reduce the need for expensive PET scans, offering better motion tolerance, improved image quality, and increased sensitivity to changes in Aβ aggregation size. Additionally, its non-invasive nature allows for repeat scans, enabling us to study variability, reliability, and long-term changes in AD mechanisms.