Single-cell analysis of mtDNA deletion levels in sporadic amyotrophic lateral sclerosis

Neuroreport. 2004 Apr 29;15(6):939-43. doi: 10.1097/00001756-200404290-00002.


One possible cause for the neuronal loss in sporadic amyotrophic lateral sclerosis (S-ALS) is an increase of free radicals, which may produce oxidative damage to susceptible biomolecules, which, in turn, can damage the mitochondrial DNA (mtDNA). Following laser microdissection of single motor neurons from paraffin-embedded autopsy tissue, we analyzed the presence of a common mtDNA deletion, the 5 kb common deletion (CD). Spinal cord neurons showed slightly higher CD detection rate in patients than controls (94% vs 75%). No significant differences were found between patients and controls for neurons derived from other motor or non-motor regions. A PCR assay of serial DNA dilutions (10-fold) showed no CD level differences between motor neurons in S-ALS and controls. These data suggest that neuronal death in S-ALS is not associated with significant accumulation of mtDNA deletions.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology*
  • Brain / metabolism
  • Brain / pathology
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Female
  • Gene Deletion*
  • Humans
  • Male
  • Microdissection / methods
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Reactive Oxygen Species / metabolism
  • Spinal Cord / metabolism
  • Spinal Cord / pathology


  • DNA, Mitochondrial
  • Reactive Oxygen Species