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Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.

ABSTRACT: Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChip v2.0 array. Our analysis identified 270 significantly different nps which, with one exception, showed an increased contribution of non-reference alleles in AD patients. Principal component analysis (PCA) and cluster analysis showed that five of these nps could discriminate AD from control subjects with 80% of cases correctly classified. Our data support the hypothesis of mtDNA alterations as an important factor in the etiology of AD.

SUBMITTER: Casoli T

PROVIDER: S-EPMC4292745 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Contribution of non-reference alleles in mtDNA of Alzheimer's disease patients.

Casoli Tiziana T Di Stefano Giuseppina G Spazzafumo Liana L Balietti Marta M Giorgetti Belinda B Giuli Cinzia C Postacchini Demetrio D Fattoretti Patrizia P Conti Fiorenzo F

Annals of clinical and translational neurology 20140311 4

Many observations suggest that mutations of mitochondrial DNA (mtDNA) could be responsible for the neurodegenerative changes of Alzheimer's disease (AD). Here we examined the signal intensity of the four alleles of each mtDNA nucleotide position (np) in whole blood of AD patients and age-matched controls using MitoChip v2.0 array. Our analysis identified 270 significantly different nps which, with one exception, showed an increased contribution of non-reference alleles in AD patients. Principal ...[more]

PMID: 25590040

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

Project description: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.

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