Longitudinal MRI Assessment of ARIA in 22 month old PS2APP Mice Treated with Anti-Amyloid-ß Antibodies

Motivation: Anti-amyloid-ß (anti-Aß) therapy development for Alzheimer's disease is hindered by the lack of an effective animal model for amyloid-related imaging abnormalities (ARIA), a major safety concern. Goal(s): This study aims to develop a preclinical mouse model replicating ARIA seen in human treatments to assess ARIA risks early in drug development. Approach: Using 22-month-old PS2APP mice treated with anti-Aß, we conducted weekly MRI scans over 10 weeks to detect ARIA, with plaque reduction assessed at study end. Results: ARIA was successfully induced, with ARIA-E showing delayed onset and transient behavior, and ARIA-H detected. Treated mice also exhibited significant plaque reduction, demonstrating anti-Aß activity. Impact: This study demonstrates that ARIA-E and ARIA-H can be induced in aged PS2APP mice, replicating key human dynamics. This model enables preclinical ARIA evaluation, potentially accelerating development of safer anti-amyloid-ß therapies for Alzheimer's disease.