A systematic review of suggested molecular strata, biomarkers and their tissue sources in ALS

Geetha Vijayakumar, Vanessa Milla, Cynthia Stafford, AJ Bjourson, William Duddy, Stephanie Duguez

Research output: Contribution to journalReview articlepeer-review

57 Citations (Scopus)
56 Downloads (Pure)


Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is an incurable neurodegenerative condition, characterized by the loss of upper and lower motor neurons. It affects 1–1.8/100,000 individuals worldwide, and the number of cases is projected to increase as the population ages. Thus, there is an urgent need to identify both therapeutic targets and disease-specific biomarkers–biomarkers that would be useful to diagnose and stratify patients into different subgroups for therapeutic strategies, as well as biomarkers to follow the efficacy of any treatment tested during clinical trials. There is a lack of knowledge about pathogenesis and many hypotheses. Numerous “omics” studies have been conducted on ALS in the past decade to identify a disease-signature in tissues and circulating biomarkers. The first goal of the present review was to group the molecular pathways that have been implicated in monogenic forms of ALS, to enable the description of patient strata corresponding to each pathway grouping. This strategy allowed us to suggest 14 strata, each potentially targetable by different pharmacological strategies. The second goal of this review was to identify diagnostic/prognostic biomarker candidates consistently observed across the literature. For this purpose, we explore previous biomarker-relevant “omics” studies of ALS and summarize their findings, focusing on potential circulating biomarker candidates. We systematically review 118 papers on biomarkers published during the last decade. Several candidate markers were consistently shared across the results of different studies in either cerebrospinal fluid (CSF) or blood (leukocyte or serum/plasma). Although these candidates still need to be validated in a systematic manner, we suggest the use of combinations of biomarkers that would likely reflect the “health status” of different tissues, including motor neuron health (e.g., pNFH and NFL, cystatin C, Transthyretin), inflammation status (e.g., MCP-1, miR451), muscle health (miR-338-3p, miR-206) and metabolism (homocysteine, glutamate, cholesterol). In light of these studies and because ALS is increasingly perceived as a multi-system disease, the identification of a panel of biomarkers that accurately reflect features of pathology is a priority, not only for diagnostic purposes but also for prognostic or predictive applications.

Original languageEnglish
Article number400
Number of pages17
JournalFrontiers in Neurology
Issue numberMAY
Early online date14 May 2019
Publication statusPublished (in print/issue) - 14 May 2019


  • ALS
  • Circulating biomarkers
  • Motor neuron disease
  • Multi-system biomarkers
  • Patients stratification
  • motor neuron disease
  • circulating biomarkers
  • multi-system biomarkers
  • patients stratification


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