Increased contribution of non-reference alleles in mitochondrial DNA (mtDNA) of Alzheimer's disease (AD) patients

Many observations suggest that mutations of mtDNA could be responsible of the neurodegenerative changes associated with AD. We examined the signal intensity of the four alleles for each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls utilizing a resequencing array, the MitoChip v2.0, and identified 275 statistically different nps which all, with the exception of one, showed an increased contribution of non-reference alleles for AD patients. PCA and cluster analysis showed that 5 of these nps, characterized by low-level heteroplasmy, could discriminate AD from control subjects with 80% of cases correctly classified. This study included a total of 18 AD patients and 18 age-matched controls. Data acquisition was performed using the Affymetrix Genechip Command Console (AGCC) software and data analysis was carried out with GSEQ 4.1.