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Abstract #0535

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

Man Kin Choy1, Monica Xiong2, William J Meilandt2, Rohan S Virgincar3, Jose Imperio2, Steve Vito2, Tiffany Wu2, Filipp Frank4, Preeti Sharma4, Chris Bohlen2, Robby M Weimer3, and Luke Xie3
1Translational Imaging, Genentech, Menlo Park, CA, United States, 2Neuroscience, Genentech, South San Francisco, CA, United States, 3Translational Imaging, Genentech, South San Francisco, CA, United States, 4Antibody Engineering, Genentech, South San Francisco, CA, United States

Synopsis

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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