Keywords: Biology, Models, Methods, Drug Development
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.
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