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A curious concept of CNS clearance

arising from A. Miao et al. Nature Neuroscience https://doi.org/10.1038/s41593-024-01638-y (2024)

Over the past decade, multiple lines of research have shown that sleep decreases amyloid-β and tau burden compared with wakefulness, and glymphatic clearance is increased during sleep in both human and mouse brains1,2,3,4,5,6. A recent study by Miao et al.7 has questioned these findings. We here raise concerns regarding experimental methodology, analytical rigor, and theoretical and mathematical assumptions in the Miao et al.7 study. The conclusion of that study—brain clearance is reduced during sleep and anesthesia—is not supported by the data presented.

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Fig. 1: Discrepancy between flow velocity model and actual velocity.

Fig. 2: Data visualization, unequal sampling and improper statistical analysis may cause interpretation errors in diurnal variation of diffusion.

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Acknowledgements

This work was supported by National Institutes of Health grant R01AT012312 (to M.N.); NINDS R01AT011439 (to M.N.); U19 NS128613 (to M.N.); the Simons Foundation (to M.N.); Novo Nordisk Foundation NNF20OC0066419 (to M.N.); the Lundbeck Foundation R386-2021-165 (M.N.); The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.N.); JPND/HBCI 1098-00030B (to M.N.); JPND/Good Vibes 2092-00006B (to M.N.); DOD W911NF2110006 (to M.N.); Independent Research Fund Denmark 3101-00282B (to M.N.); US Army Research Office grants MURI W911NF1910280 (to M.N.); and American Heart Association Career Development Award 941177 (L.M.H.).

Author information

Author notes

These authors contributed equally: Virginia Plá, Erik Kroesbergen.

Authors and Affiliations

Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark

Virginia Plá, Erik Kroesbergen, Saiyue Deng, Tina Esmail, Ryszard Stefan Gomolka, Yuki Mori, Steven A. Goldman & Maiken Nedergaard

Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, USA

Michael J. Giannetto, Lauren M. Hablitz, Evan Newbold, Antonio Ladrón-de-Guevara, Steven A. Goldman & Maiken Nedergaard

Department of Mechanical Engineering, University of Rochester, Rochester, NY, USA

Douglas H. Kelley & John H. Thomas

Authors

Virginia Plá

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