Misfolded SOD1 is not a primary component of sporadic ALS

Acta Neuropathol. 2017 Jul;134(1):97-111. doi: 10.1007/s00401-017-1688-8. Epub 2017 Feb 28.


A common feature of inherited and sporadic ALS is accumulation of abnormal proteinaceous inclusions in motor neurons and glia. SOD1 is the major protein component accumulating in patients with SOD1 mutations, as well as in mutant SOD1 mouse models. ALS-linked mutations of SOD1 have been shown to increase its propensity to misfold and/or aggregate. Antibodies specific for monomeric or misfolded SOD1 have detected misfolded SOD1 accumulating predominantly in spinal cord motor neurons of ALS patients with SOD1 mutations. We now use seven different conformationally sensitive antibodies to misfolded human SOD1 (including novel high affinity antibodies currently in pre-clinical development) coupled with immunohistochemistry, immunofluorescence and immunoprecipitation to test for the presence of misfolded SOD1 in high quality human autopsy samples. Whereas misfolded SOD1 is readily detectable in samples from patients with SOD1 mutations, it is below detection limits for all of our measures in spinal cord and cortex tissues from patients with sporadic or non-SOD1 inherited ALS. The absence of evidence for accumulated misfolded SOD1 supports a conclusion that SOD1 misfolding is not a primary component of sporadic ALS.

Keywords: Amyotrophic lateral sclerosis (ALS); Human patients; Misfolding; Neurodegeneration; Neuropathology; Sporadic (SALS); Superoxide dismutase (SOD1).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Disease Models, Animal
  • Female
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Male
  • Mice, Transgenic
  • Middle Aged
  • Protein Folding
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism*
  • Young Adult


  • SOD1 protein, human
  • Superoxide Dismutase-1