40 Years of CSF Toxicity Studies in ALS: What Have We Learnt About ALS Pathophysiology?

Koy Chong Ng Kee Kwong, Pratap K. Harbham, Bhuvaneish T. Selvaraj, Jenna M. Gregory, Suvankar Pal, Giles E. Hardingham, Siddharthan Chandran, Arpan R. Mehta (Lead / Corresponding author)

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Based on early evidence of in vitro neurotoxicity following exposure to serum derived from patients with amyotrophic lateral sclerosis (ALS), several studies have attempted to explore whether cerebrospinal fluid (CSF) obtained from people with ALS could possess similar properties. Although initial findings proved inconclusive, it is now increasingly recognized that ALS-CSF may exert toxicity both in vitro and in vivo. Nevertheless, the mechanism underlying CSF-induced neurodegeneration remains unclear. This review aims to summarize the 40-year long history of CSF toxicity studies in ALS, while discussing the various mechanisms that have been proposed, including glutamate excitotoxicity, proteotoxicity and oxidative stress. Furthermore, we consider the potential implications of a toxic CSF circulatory system in the pathophysiology of ALS, and also assess its significance in the context of current ALS research.

Original languageEnglish
Article number647895
Number of pages12
JournalFrontiers in Molecular Neuroscience
Early online date18 Mar 2021
Publication statusPublished - 2021


  • amyotrophic lateral sclerosis
  • cerebrospinal fluid
  • motor neuron disease
  • neurodegeneration
  • pathophysiology
  • toxicity


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