Heteroplasmy of mitochondrial D310 mononucleotide repeat region in the blood of patients with Alzheimer's disease.

There is increasing evidence of oxidative stress in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Because mitochondrial DNA (mtDNA) is susceptible to oxidative damage, somatic mtDNA mutations may be induced by oxidative stress. Most of the studies examining mitochondrial mutations have been performed on postmortem brain tissues of AD patients. This study examined peripheral blood samples of AD and MCI patients to determine if peripheral mtDNA mutations are associated with these two conditions. A total of 236 subjects, including 71 AD patients, 84 amnestic MCI patients, 41 cognitively normal aging controls, and 40 young controls, were recruited. There was heteroplasmy of the mtDNA D310 polycytosine repeat region in 37 of 71 (52.1%) AD patients and this was significantly more frequent than in MCI patients (31.0%), normal aging (31.7%), and young controls (27.5%). However, subjects with amnestic MCI did not have a significantly higher rate of heteroplasmy in D310 than cognitively normal elderly subjects. The heteroplasmic alterations of D310 were more frequently in subjects with a larger number of polycytosine repetitions. Insertion of cytosine was the most common mutation type. The results suggest that mutations of mtDNA 310 region are frequently present in the peripheral blood of AD patients. Further prospective investigations to determine if MCI subjects with D310 mutations develop AD is warranted.