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Distinct forms of amyloid-β moderate sleep duration through NAD + -linked redox metabolism in Alzheimer’s disease
Abstract
Sleep disruptions precede a clinical diagnosis of Alzheimer’s disease (AD) by several years. However, how AD pathologies affect sleep remains unclear. Here, we integrate epidemiological data with insights from Drosophila models of AD to investigate how AD progression could be linked to sleep disruption. We found that individuals with a high risk of AD report a shorter sleep duration than do those with a clinical diagnosis of AD. We showed that the expression of different forms of amyloid-β in flies can replicate these variations in sleep duration. Analysis of the metabolome and proteome of these flies revealed distinct changes in NAD + -linked redox metabolism and levels of hyperkinetic (Hk), a redox-sensing sleep homeostat. We showed that the genetic upregulation of Hk is neuroprotective and increased KCNAB2 expression in the brain decreases AD risk in humans. Overall, our data provides a new mechanism linking the disruption of NAD + -linked redox sensing and sleep disruption in AD.
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“Individually, three of the included studies found a non-statistically significant difference in overall PSQI score between the concussed and non-concussed participants [43,48,49].”
From Concussion Disrupts Sleep in Adolescents: A Systematic Review and Meta-Analysis (2025) · cites this paper as [49]
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“both of which influence sleep”
From Concussion Disrupts Sleep in Adolescents: A Systematic Review and Meta-Analysis (2025) · cites this paper as [49]
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“Albicini and colleagues [49] reported an effect size that was most distinct from others (Figure 3a).”
From Concussion Disrupts Sleep in Adolescents: A Systematic Review and Meta-Analysis (2025) · cites this paper as [49]
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“the daytime dysfunction component of the PSQI was the most consistently reported altered component, even in cases where no overall difference in PSQI was found [48,49].”
From Concussion Disrupts Sleep in Adolescents: A Systematic Review and Meta-Analysis (2025) · cites this paper as [49]
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Cited by
Concussion Disrupts Sleep in Adolescents: A Systematic Review and Meta-Analysis
Noordeen, S., Wang, P., Strazda, A. E., Arany, E. S., Ergisi, M., Yeo, L. J., Popovic, R., Mahendran, A., Khawaja, M., Grover, K., et al. (2025) · Clocks & Sleep · doi:10.3390/clockssleep7030046 · Cited by 2
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Metadata
- Authors
- Yu, Y., Fedele, G., Celardo, I., Zhou, L., Zhi Tan, B. W., Loh, S. H. Y., & Martins, L. M.
- Publisher
- openRxiv
- Published
- 2025-03-03
- Cited by
- 3
- References
- 14
- Type
- Preprint
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