Mitochondrial DNA mutations increase in early stage Alzheimer disease and are inconsistent with oxidative damage.
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.
Department of Pathology, University of Washington, Seattle, WA.
Jake G
JG
Hoekstra
Department of Pathology, University of Washington, Seattle, WA.
Michael J
MJ
Hipp
Department of Pathology, Stanford University, Palo Alto, CA.
Thomas J
TJ
Montine
Department of Pathology, University of Washington, Seattle, WA.
Scott R
SR
Kennedy
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D018384:Oxidative Stress; D010296:Parietal Lobe / Q000378:metabolism
D004272:DNA, Mitochondrial