Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease

Elizabeth M. Ellison; Erin L. Abner; Mark A. Lovell

doi:10.1111/jnc.13912

Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease

Elizabeth M. Ellison, Erin L. Abner, Mark A. Lovell

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late onset Alzheimer's disease, frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). Repeated measures analyses of the data show significant alterations in 5-mC and 5-hmC in early stages of Alzheimer's disease (PCAD and MCI), as well as FTLD and DLB subjects, across multiple regions of the brain. These data suggest alterations in epigenetic regulation of genes may play an early role in the progression of AD as well as other types of neurodegeneration. (Figure presented.).

Original language	English
Pages (from-to)	383-394
Number of pages	12
Journal	Journal of Neurochemistry
Volume	140
Issue number	3
DOIs	https://doi.org/10.1111/jnc.13912
State	Published - Feb 1 2017

Bibliographical note

Funding Information:
This work was supported by National Institute of Health grants 5P01-AG05119 and P30-AG028383, as well as a grant from Alltech Biotechnology. The authors thank Dr Peter Nelson, Dr Steven Scheff, Ms. Sonya Anderson, and Ms. Ela Patel from the UK-ADC Clinical and Neuropathology Cores, and Mr. Timothy Shannon from the Data Management and Statistics Core for subject data, and Ms. Paula Thomason for editorial assistance. The authors report no conflict of interest in the research or data described in this article. All experiments were conducted in compliance with the ARRIVE guidelines.

Publisher Copyright:
© 2016 International Society for Neurochemistry

Keywords

5-hydroxymethylcytosine
5-methylcytosine
Alzheimer's disease
epigenetic

ASJC Scopus subject areas

Biochemistry
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jnc.13912

Cite this

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title = "Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease",

abstract = "Epigenetic modifications to cytosine are known to alter transcriptional states and deregulate gene expression in cancer, embryonic development, and most recently in neurodegeneration. To test the hypothesis that global levels of cytosine modification are altered throughout the progression of Alzheimer's disease, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were quantified in DNA extracted from tissue specimens of four brain regions (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late onset Alzheimer's disease, frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB). Repeated measures analyses of the data show significant alterations in 5-mC and 5-hmC in early stages of Alzheimer's disease (PCAD and MCI), as well as FTLD and DLB subjects, across multiple regions of the brain. These data suggest alterations in epigenetic regulation of genes may play an early role in the progression of AD as well as other types of neurodegeneration. (Figure presented.).",

keywords = "5-hydroxymethylcytosine, 5-methylcytosine, Alzheimer's disease, epigenetic",

author = "Ellison, {Elizabeth M.} and Abner, {Erin L.} and Lovell, {Mark A.}",

note = "Funding Information: This work was supported by National Institute of Health grants 5P01-AG05119 and P30-AG028383, as well as a grant from Alltech Biotechnology. The authors thank Dr Peter Nelson, Dr Steven Scheff, Ms. Sonya Anderson, and Ms. Ela Patel from the UK-ADC Clinical and Neuropathology Cores, and Mr. Timothy Shannon from the Data Management and Statistics Core for subject data, and Ms. Paula Thomason for editorial assistance. The authors report no conflict of interest in the research or data described in this article. All experiments were conducted in compliance with the ARRIVE guidelines. Publisher Copyright: {\textcopyright} 2016 International Society for Neurochemistry",

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Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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