A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β

Jeffrey J. Iliff; Minghuan Wang; Yonghong Liao; Benjamin A. Plogg; Weiguo Peng; Georg A. Gundersen; Helene Benveniste; G. Edward Vates; Rashid Deane; Steven A. Goldman; Erlend A. Nagelhus; Maiken Nedergaard

doi:10.1126/scitranslmed.3003748

Research ArticleCerebrospinal Fluid Circulation

A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β

Jeffrey J. Iliff¹,*,
Minghuan Wang¹,²,
Yonghong Liao¹,
Benjamin A. Plogg¹,
Weiguo Peng¹,
Georg A. Gundersen³,⁴,
Helene Benveniste⁵,⁶,
G. Edward Vates¹,
Rashid Deane¹,
Steven A. Goldman¹,⁷,
Erlend A. Nagelhus³,⁴ and
Maiken Nedergaard¹,*

¹Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.
²Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
³Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway.
⁴Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
⁵Department of Radiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.
⁶Department of Anesthesiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.
⁷Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.

↵*To whom correspondence should be addressed. E-mail: jeffrey_iliff{at}urmc.rochester.edu (J.J.I.); nedergaard{at}urmc.rochester.edu (M.N.)

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Science Translational Medicine 15 Aug 2012:
Vol. 4, Issue 147, pp. 147ra111
DOI: 10.1126/scitranslmed.3003748

Jeffrey J. Iliff

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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For correspondence: jeffrey_iliff@urmc.rochester.edu nedergaard@urmc.rochester.edu

Minghuan Wang

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

2Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

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Yonghong Liao

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Benjamin A. Plogg

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Weiguo Peng

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Georg A. Gundersen

3Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway.

4Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.

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Helene Benveniste

5Department of Radiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.

6Department of Anesthesiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.

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G. Edward Vates

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Rashid Deane

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Steven A. Goldman

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

7Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Erlend A. Nagelhus

3Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway.

4Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.

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Maiken Nedergaard

1Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA.

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For correspondence: jeffrey_iliff@urmc.rochester.edu nedergaard@urmc.rochester.edu

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Cerebrospinal fluid flows through channels around brain blood vessels that are bounded by astrocytic endfeet, mediated by water transport through aquaporin-4.

A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β

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