Common mtDNA polymorphisms and neurodegenerative disorders

Abstract

The prevalence of the late onset neurodegenerative disorders Alzheimer’s and Parkinson’s disease is increasing as the population ages. They impose a considerable health care cost, which will grow as the population continues to age. Both disorders have been associated with oxidative stress and mitochondrial dysfunction. It has been proposed that population variants of the DNA found inside the mitochondria have a role in the etiology of both these neurodegenerative disorders. We inherit our mitochondrial DNA (mtDNA) from our mothers and the variation seen is grouped into distinct lineages called haplogroups. As mtDNA in mammals does not undergo recombination, these haplogroups are stable and distinct blocks of SNP variation. mtDNA is located at the site of energy production and thus exposed to the free radicals associated with this process. This results in mtDNA having high variation within and between populations. The lack of recombination in mtDNA causes the variant correlations to be very complex, which makes the determination of the possible role of population variants in common disease difficult. There have been many studies trying to determine if mtDNA population variants play a role in neurodegenerative disorders. They have generated both positive and negative results, for the same phenotypes. After many years of work, the role of mtDNA variants in the development of either AD or PD still remains to be established conclusively. Here, we explore the reasons for the hypothesis that mtDNA population variants might play a role in AD and/or PD. Finally, we discuss how we might move from having an attractive hypothesis with some supporting evidence to a robust answer as to whether these variants play a role in neurodegenerative disorders.