Protein Aggregation MRI for Early Detection of Alzheimer’s Disease

• Applicant: Professor Dr. Moritz Zaiss
• Subject Area: Medical Physics, Biomedical Technology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567464103

Magnetic Resonance Imaging (MRI) is essential for diagnosing neurodegenerative diseases like Alzheimer’s disease (AD), but current methods primarily assess brain atrophy and white matter integrity rather than directly detecting amyloid or tau aggregates—the hallmarks of AD. While Positron Emission Tomography (PET) provides direct visualization of these aggregates, it is costly, involves radiation exposure, and not ideal for routine monitoring. To bridge this gap, we propose a novel, non-invasive imaging technique: Protein Aggregation MRI using Chemical Exchange Saturation Transfer (CEST). Protein aggregation is a fundamental process in AD pathology. Detecting these changes early, before irreversible damage occurs, could transform AD diagnosis, enabling earlier intervention and better treatment outcomes. This project pioneers aggregation-weighted CEST MRI, a novel technique with the potential of capturing molecular changes linked to protein unfolding, aggregation, and amyloid load. Previous phantom studies and animal models confirm the feasibility of detecting protein aggregation by CEST contrast changes, laying the foundation for this project. Yet, there remain several challenges: (i) high sampling – CEST MRI requires extensive spectral data, leading to long scan times. (ii) high Spatial Resolution and coverage – detecting amyloid plaques in different gray matter demands fine imaging detail and coverage of the whole brain. (iii) complex data processing: the aggregation signature is complex and needs to be robustly extracted from the CEST spectra. To overcome these challenges and realize a clinically feasible protein-aggregation MRI we want to join forces of our two research groups with complementary strengths. The Zaiss Lab (UKER, Germany) and Park Lab (SKKU, Korea) bring together synergistic expertise in CEST sequence optimization, AI-based spectral analysis, and ultra-fast MRI acquisition. Our key objectives are: (i) Developing a high-sensitivity, 3D whole-brain CEST MRI technique for protein aggregation detection. (ii) Building a spectral database of healthy and AD subjects to refine in vivo aggregation signatures at 7T and at 3T (iii) Leveraging AI for rapid, high-fidelity reconstructions, ensuring clinical feasibility, and translation to 3T to broaden the potential impact of protein aggregation imaging technique. This research lays the foundation for a non-invasive, high-resolution imaging biomarker for AD—revolutionizing early diagnosis, treatment monitoring, and clinical decision-making. With novel AD medication around the corner, future applications could seamlessly integrate this technique into large-scale clinical trials and routine imaging protocols, particularly in assessing responses to novel anti-amyloid therapies. By making protein aggregation visible through MRI, this project could fundamentally change how we detect, track, and treat Alzheimer’s disease—unlocking new possibilities for precision medicine in neurodegeneration.

• DFG Programme: Research Grants
• International Connection: South Korea
• Partner Organisation: National Research Foundation of Korea, NRF
• Cooperation Partner: Professor Jaeseok Park, Ph.D.