Repetitive induction of a hibernation-like brain state slows amyloid pathology

Alzheimer’s disease (AD) is characterized by the gradual accumulation of amyloid pathology before the onset of cognitive impairment, yet effective strategies to alter disease progression remain limited. Here, we tested whether induction of a hibernation-like physiological state can slow amyloid pathology in an AD mouse model. To achieve sustained effects, we developed a protocol for repeated induction of a hypometabolic/hypothermic state and found that it significantly slowed plaque accumulation in a duration-dependent manner. This intervention also attenuated neuroinflammation and the formation of dystrophic neurites associated with plaques. Notably, this approach does not target specific molecular pathways but instead modulates global brain state. Our findings establish a proof-of-concept for a brain-state– based therapeutic paradigm for modifying disease progression in AD.