Frontiers in Aging Neuroscience (Jul 2015)

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

  • Tiziana eCasoli,
  • Liana eSpazzafumo,
  • Giuseppina eDi Stefano,
  • Fiorenzo eConti,
  • Fiorenzo eConti

DOI
https://doi.org/10.3389/fnagi.2015.00142
Journal volume & issue
Vol. 7

Abstract

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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.

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