Role of diffuse low-level heteroplasmy of mitochondrial DNA in Alzheimer's disease neurodegeneration

Tiziana Casoli, Liana Spazzafumo, Giuseppina Di Stefano, Fiorenzo Conti

Research output: Contribution to journalArticlepeer-review


Alzheimer's disease (AD) is the most common form of dementia in the elderly. The vast majority of cases are not linked to a known genetic defect and the molecular mechanisms underlying AD pathogenesis are still elusive. Evidence suggests that mitochondrial dysfunction is a prominent feature of the disease, and that mitochondrial DNA (mtDNA) alterations may represent a possible starting point of the pathophysiological cascade. Although specific mtDNA alterations have been reported in AD patients both in brain and peripheral tissues, such as D-loop mutations, 4977-bp deletion and poly-C tract D310 cytosine insertion, a generalized subtle allelic shift has also been demonstrated. This shift is significant for a few nucleotide positions (nps), but it is also detectable for most nps, although at a lower level. As single allelic substitutions can unlikely be determinant, it is proposed that the combination of all of them could lead to a less efficient oxidative phosphorylation, thus influencing AD development and course.

Original languageEnglish
Article number142
JournalFrontiers in Aging Neuroscience
Issue numberJUL
Publication statusPublished - 2015


  • Aging
  • Allele
  • Alzheimer's disease
  • Heteroplasmy
  • MitoChip
  • mtDNA
  • Mutation

ASJC Scopus subject areas

  • Ageing
  • Cognitive Neuroscience


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