Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Sex-specific acceleration of Alzheimer's pathogenesis by chronic sleep-deprivation.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Wear Darcy, Morrone Christopher Daniel, Simpson Dominic, Liu Fang, Hussaini Syed Abid, Yu Wai Haung
Аннотация
INTRODUCTION: Sleep impairments likely contribute to Alzheimer's pathology, though specific contributions to disease progression are incompletely understood. We propose that autophagic impairment is associated with chronic sleep disruption and examine how sleep loss and stress influence disease development, including having impacts on proteostasis, cognition, and neural circuitry.
METHODS: We sleep-disrupted 6-month-old APPNL-G-F mice for 2 weeks and behaviorally assessed sleep recovery, nesting, stress, and cognition. Subsequently, we analyzed markers of Alzheimer's pathology, stress, neuroinflammation, and proteostasis in hippocampal and subcortical brain regions.
RESULTS: Sleep-deprived mice had altered sleep-related behaviors, increased stress, and signs of disease-acceleration including sex-dependent neurodegeneration, proteinopathy, and changes to autophagy and the neuroinflammatory response.
DISCUSSION: Chronic sleep disruption accelerates the pathological cascade of Alzheimer's, including cognitive impairment and Alzheimer's pathology in a sex-dependent manner. This work enhances our understanding of the sleep-stress-Alzheimer's relationship, including sex-based differences, and may point to a novel therapeutic avenue to limit Alzheimer's progression.
METHODS: We sleep-disrupted 6-month-old APPNL-G-F mice for 2 weeks and behaviorally assessed sleep recovery, nesting, stress, and cognition. Subsequently, we analyzed markers of Alzheimer's pathology, stress, neuroinflammation, and proteostasis in hippocampal and subcortical brain regions.
RESULTS: Sleep-deprived mice had altered sleep-related behaviors, increased stress, and signs of disease-acceleration including sex-dependent neurodegeneration, proteinopathy, and changes to autophagy and the neuroinflammatory response.
DISCUSSION: Chronic sleep disruption accelerates the pathological cascade of Alzheimer's, including cognitive impairment and Alzheimer's pathology in a sex-dependent manner. This work enhances our understanding of the sleep-stress-Alzheimer's relationship, including sex-based differences, and may point to a novel therapeutic avenue to limit Alzheimer's progression.