Humanized App knockin (KI) and APP transgenic mouse models mimic certain aspects of AD pathogenesis, including progressive amyloidosis, gliosis, and neuroinflammation, as well as network hyperexcitability and cognitive impairment, albeit to different degrees of severity across models and paradigms.15-27 However, our understanding of alterations in spontaneous behavior in AD models has been limited by the technical challenges of assessing non-task-oriented behavior. Here, APP is linked to Alzheimer disease.