Novel regional biomarkers of progressive brain degeneration in the TauPS2APP mouse model of Alzheimer’s Disease

Motivation: The TauPS2APP mouse is a well-established model of Alzheimer’s Disease. Traditionally, analyses focus on hippocampus and isocortex, but brain-wide analysis may yield a more comprehensive description of brain degeneration and identify additional regional biomarkers. Goal(s): Identifying robust signatures of brain degeneration resulting from amyloidosis and tauopathyApproach: We conducted a brain-wide voxel-based analysis of longitudinal MRI data from TauPS2APP mice collected from three studies (n=123). Results: We found expected and persistent hippocampal and isocortical volume differences between wildtype and TauPS2APP mice. Also, we identified progressive atrophy in caudoputamen (95% of 123 TauPS2APP mice) and expansion in subiculum/hippocampal commissures (89% of 123 mice). Impact: We identified novel and robust regional biomarkers of progressive brain degeneration in the TauPS2APP mouse model of AD. These regions are additional targets for assessing brain degeneration associated with amyloidosis and tauopathy, and for testing new therapies.