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ResearchIn-Press PreviewCell biologyNeuroscience Open Access | 10.1172/JCI182931

Sleep-wake variation in body temperature regulates tau secretion and correlates with CSF and plasma tau

Geoffrey Canet,1 Felipe Da Gama Monteiro,2 Emma Rocaboy,1 Sofia Diego-Diaz,1 Boutheyna Khelaifia,1 Kelly Godbout,1 Aymane Lachhab,1 Jessica Kim,3 Daphne I. Valencia,4 Audrey Yin,3 Hau-Tieng Wu,3 Jordan C. Howell,3 Emily Blank,3 Francis Laliberté,5 Nadia Fortin,5 Emmanuelle Boscher,5 Parissa Fereydouni-Forouzandeh,1 Stéphanie Champagne,1 Isabelle Guisle,5 Sébastien S. Hébert,5 Vincent Pernet,6 Haiyan Liu,7 William Lu,7 Ludovic Debure,3 David M. Rapoport,4 Indu Ayappa,4 Andrew W. Varga,4 Ankit Parekh,4 Ricardo S. Osorio,3 Steve Lacroix,5 Mark P. Burns,8 Brendan P. Lucey,7 Esther M. Blessing,3 and Emmanuel Planel1

1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

Find articles by Canet, G. in: JCI | PubMed | Google Scholar

1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

Find articles by Khelaifia, B. in: JCI | PubMed | Google Scholar

1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

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1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

Find articles by Blessing, E. in: JCI | PubMed | Google Scholar

1Department of Psychiatry and Neurosciences, Research Center of CHU de Québec - Laval University, Québec, Canada

2Department of Molecular Medicine, Research Center of CHU de Québec - Laval University, Québec, Canada

3Department of Psychiatry, NYU Grossman School of Medicine, New York, United States of America

4Mount Sinai Integrative Sleep Center, Division of Pulmonary, Critical Care,, Icahn School of Medicine at Mount Sinai, New York, United States of America

5Neurosciences Axis, Research Center of CHU de Québec - Laval University, Québec, Canada

6Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

7Department of Neurology, Washington University School of Medicine, St. Louis, United States of America

8Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America

Find articles by Planel, E. in: JCI | PubMed | Google Scholar

Published February 4, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI182931.
Copyright © 2025, Canet et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 4, 2025 - Version history
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Abstract

Sleep disturbance is bidirectionally associated with increased risks of Alzheimer’s disease and other tauopathies. While the sleep-wake cycle regulates interstitial and cerebrospinal fluid (CSF) tau levels, the underlying mechanisms remain unknown. Understanding these mechanisms is crucial given evidence indicates that tau pathology spreads through neuron-to-neuron transfer, involving the secretion and internalization of pathological tau forms. Here, we combine in vitro, in vivo and clinical methods to reveal a pathway by which changes in body temperature (BT) over the sleep-wake cycle modulate extracellular tau levels. In mice, higher BT during wakefulness and sleep-deprivation increased CSF and plasma tau levels, while also upregulating unconventional protein secretion pathway-I (UPS-I) components, including (i) intracellular tau dephosphorylation, (ii) caspase-3-mediated cleavage of tau (TauC3) and (iii) its membrane translocation through binding to PIP2 and syndecan-3. In humans, the increase in CSF and plasma tau levels observed post-wakefulness correlated with BT increase during wakefulness. By demonstrating that sleep-wake variation in BT regulates extracellular tau levels, our findings highlight the importance of thermoregulation in linking sleep disturbances to tau-mediated neurodegeneration, and the preventative potential of thermal interventions.

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