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Defining novel functions for cerebrospinal fluid in ALS pathophysiology

Authors
  • Ng Kee Kwong, Koy Chong1, 2, 3
  • Mehta, Arpan R.1, 2, 3, 3, 4
  • Nedergaard, Maiken5, 6
  • Chandran, Siddharthan1, 2, 3, 3, 7
  • 1 UK Dementia Research Institute at University of Edinburgh, Edinburgh, UK , Edinburgh (United Kingdom)
  • 2 University of Edinburgh, Edinburgh bioQuarter, Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK , Edinburgh (United Kingdom)
  • 3 University of Edinburgh, Edinburgh, UK , Edinburgh (United Kingdom)
  • 4 University of Oxford, Oxford, UK , Oxford (United Kingdom)
  • 5 University of Copenhagen, Copenhagen, Denmark , Copenhagen (Denmark)
  • 6 University of Rochester Medical Center, Rochester, NY, USA , Rochester (United States)
  • 7 inStem, Bangalore, India , Bangalore (India)
Type
Published Article
Journal
Acta Neuropathologica Communications
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Aug 20, 2020
Volume
8
Issue
1
Identifiers
DOI: 10.1186/s40478-020-01018-0
Source
Springer Nature
Keywords
License
Green

Abstract

Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer’s disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.

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