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Mitochondrial DNA mutations increase in early stage Alzheimer disease and are inconsistent with oxidative damage
Author(s) -
Hoekstra Jake G.,
Hipp Michael J.,
Montine Thomas J.,
Kennedy Scott R.
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24709
Subject(s) - mitochondrial dna , mutation , biology , genetics , oxidative stress , somatic cell , human mitochondrial genetics , dna damage , mitochondrion , oxidative phosphorylation , oxidative damage , disease , phenotype , gene , dna , medicine , endocrinology , biochemistry
Mitochondrial dysfunction and oxidative damage are commonly associated with early stage Alzheimer disease (AD). The accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been hypothesized to be a driver of these phenotypes, but the detection of increased mutation loads has been difficult due to a lack of sensitive methods. We used an ultrasensitive next generation sequencing technique to measure the mutation load of the entire mitochondrial genome. Here, we report a significant increase in the mtDNA mutation frequency in the hippocampus of early stage AD, with the cause of these mutations being consistent with replication errors and not oxidative damage. Ann Neurol 2016;80:301–306