Cited by 192Epigenetics and DNA MethylationAlzheimer's disease research and treatmentsMitochondrial Function and Pathology

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

Open access
Blanch, Marta, Mosquera, Jose Luis, Ansoleaga, Belén, Ferrer, Isidre, Barrachina, Marta·2016·The American Journal of Pathology

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.ajpath.2015.10.004

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Jellinger K, Mizuno Y: Parkinson's disease. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders. Edited by Dickson DW. Basel, ISN Neuropath Press, 2003, pp 159e187

Cited by

Sorted by citations

Authors
Blanch, M., Mosquera, J. L., Ansoleaga, B., Ferrer, I., & Barrachina, M.
Affiliations
Bellvitge University Hospital (ES)
Corresponding author
Barrachina, Marta
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2016-02
Volume
186
Issue
2
Pages
385-397
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2225347805
Cited by
192
References
67
Citations by year
2026: 5 · 2025: 10 · 2024: 28 · 2023: 13 · 2022: 24 · 2021: 28 · 2020: 33 · 2019: 16 · 2018: 10 · 2017: 18 · 2016: 7
FWCI
8.83
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Funders
  • European Commission (278486)
  • Instituto de Salud Carlos III (PI14/, PI14/00268)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mitochondrial DNA methylation, 5-methylcytosine, Alzheimer's disease, Parkinson's disease, mitochondrial dysfunction, entorhinal cortex, substantia nigra, D-loop, Braak stages, neurodegeneration, epigenetic regulation
MeSH terms
Alzheimer Disease, Animals, Brain, Disease Models, Animal, DNA, Mitochondrial, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Parkinson Disease, Amyloid beta-Protein Precursor, DNA Methylation, Epigenesis, Genetic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review