Mitochondrial DNA deletions/rearrangements in parkinson disease and related neurodegenerative disorders

J Neuropathol Exp Neurol. 2002 Jul;61(7):634-9. doi: 10.1093/jnen/61.7.634.


Inhibition of mitochondrial respiratory chain function may contribute to dopaminergic neurodegeneration in the substantia nigra (SN) of patients with Parkinson disease (PD). Since large-scale structural changes (e.g. deletions and rearrangements in mitochondrial DNA [mtDNA]) have been associated with mitochondrial dysfunction, we tested the hypothesis that increased total mtDNA deletions/rearrangements are associated with neurodegeneration in PD. This study employed a well-established technique, long-extension polymerase chain reaction (LX-PCR), to detect the multiple mtDNA deletions/rearrangements in the SN of patients with PD, multiple system atrophy (MSA), dementia with Lewy bodies (DLB), Alzheimer disease (AD), and age-matched controls. We also compared the total mtDNA deletions/rearrangements in different brain regions of PD patients. The results demonstrated that both the number and variety of mtDNA deletions/rearrangements were selectively increased in the SN of PD patients compared to patients with other movement disorders as well as patients with AD and age-matched controls. In addition, increased mtDNA deletions/rearrangements were observed in other brain regions in PD patients, indicating that mitochondrial dysfunction is not just limited to the SN of PD patients. These data suggest that accumulation of total mtDNA deletions/rearrangements is a relatively specific characteristic of PD and may be one of the contributing factors leading to mitochondrial dysfunction and neurodegeneration in PD.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • DNA Damage / genetics*
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Female
  • Gene Deletion*
  • Humans
  • Lewy Body Disease / genetics
  • Lewy Body Disease / metabolism
  • Lewy Body Disease / pathology
  • Male
  • Middle Aged
  • Multiple System Atrophy / genetics
  • Multiple System Atrophy / metabolism
  • Multiple System Atrophy / pathology
  • Mutation / genetics*
  • Neurons / metabolism*
  • Neurons / pathology
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Polymerase Chain Reaction
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology
  • Substantia Nigra / physiopathology


  • DNA, Mitochondrial