Amyotrophic lateral sclerosis and cerebellum

Sci Rep. 2022 Jul 22;12(1):12586. doi: 10.1038/s41598-022-16772-5.

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating, heterogeneous neurodegenerative neuromuscular disease that leads to a fatal outcome within 2-5 years, and yet, a precise nature of the association between its major phenotypes and the cerebellar role in ALS pathology remains unknown. Recently, repeat expansions in several genes in which variants appreciably contribute to cerebellar pathology, including C9orf72, NIPA1, ATXN2 and ATXN1, have been found to confer a significant risk for ALS. To better define this relationship, we performed MAGMA gene-based analysis and tissue enrichment analysis using genome-wide association study summary statistics based on a study of 27,205 people with ALS and 110,881 controls. Our preliminary results imply a striking cerebellar tissue specificity and further support increasing calls for re-evaluation of the cerebellar role in the ALS pathology.

MeSH terms

  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / pathology
  • C9orf72 Protein / genetics
  • Cerebellum / pathology
  • DNA Repeat Expansion
  • Genome-Wide Association Study
  • Humans

Substances

  • C9orf72 Protein