Format

Send to

Choose Destination
Am J Pathol. 2016 Feb;186(2):385-97. doi: 10.1016/j.ajpath.2015.10.004.

Altered Mitochondrial DNA Methylation Pattern in Alzheimer Disease-Related Pathology and in Parkinson Disease.

Author information

1
Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain.
2
Department of Statistics, University of Barcelona, Barcelona, Spain.
3
Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain; Networked Biomedical Research Centre for NeuroDegenerative Disorders (CIBERNED), Madrid, Spain; Departament of Pathology and Experimental Therapeutics, University of Barcelona, L'Hospitalet de Llobregat, Spain.
4
Institute of Neuropathology, Bellvitge University Hospital (Bellvitge Biomedical Research Institute) IDIBELL, L'Hospitalet de Llobregat, Spain; Networked Biomedical Research Centre for NeuroDegenerative Disorders (CIBERNED), Madrid, Spain. Electronic address: mbarrachina@idibell.cat.

Abstract

Mitochondrial dysfunction is linked with the etiopathogenesis of Alzheimer disease and Parkinson disease. Mitochondria are intracellular organelles essential for cell viability and are characterized by the presence of the mitochondrial (mt)DNA. DNA methylation is a well-known epigenetic mechanism that regulates nuclear gene transcription. However, mtDNA methylation is not the subject of the same research attention. The present study shows the presence of mitochondrial 5-methylcytosine in CpG and non-CpG sites in the entorhinal cortex and substantia nigra of control human postmortem brains, using the 454 GS FLX Titanium pyrosequencer. Moreover, increased mitochondrial 5-methylcytosine levels are found in the D-loop region of mtDNA in the entorhinal cortex in brain samples with Alzheimer disease-related pathology (stages I to II and stages III to IV of Braak and Braak; n = 8) with respect to control cases. Interestingly, this region shows a dynamic pattern in the content of mitochondrial 5-methylcytosine in amyloid precursor protein/presenilin 1 mice along with Alzheimer disease pathology progression (3, 6, and 12 months of age). Finally, a loss of mitochondrial 5-methylcytosine levels in the D-loop region is found in the substantia nigra in Parkinson disease (n = 10) with respect to control cases. In summary, the present findings suggest mtDNA epigenetic modulation in human brain is vulnerable to neurodegenerative disease states.

PMID:
26776077
DOI:
10.1016/j.ajpath.2015.10.004
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center