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Repetitive Hibernation-Like State Suppresses the Progression of Amyloid Pathology

Oomoto, I.; Huang, Y.; Odagawa, M.; Sakurai, T.; Suganawa, G. A.; Sasaguri, H.; Murayama, M.

2025-12-26 neuroscience
10.64898/2025.12.26.694269 bioRxiv
Show abstract

Alzheimers disease (AD) is known to exhibit amyloid pathology years before the onset of cognitive impairment. While early detection and pathological modification are considered essential for suppressing or preventing disease progression, effective strategies remain elusive. Here, we investigated whether inducing a hibernation-like state via Q neuron-induced hypometabolism/hypothermia state (QIH) suppresses the progression of early amyloid pathology in AD model mice. To maximize the total duration of QIH, we established and implemented a repetitive QIH (rQIH) protocol. Using 82E1 antibody immunostaining, we found that rQIH significantly reduced early amyloid plaque burden, and the magnitude of this suppression was positively correlated with rQIH duration. rQIH also decreased the formation of dystrophic neurites surrounding plaques. These findings demonstrate that a hibernation-like physiological state can attenuate early amyloid pathology, providing a potential foundation for future hibernation-based therapeutic strategies for AD.

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