Epigenetic changes in the progression of Alzheimer's disease

M. A. Bradley-Whitman; M. A. Lovell

doi:10.1016/j.mad.2013.08.005

Epigenetic changes in the progression of Alzheimer's disease

M. A. Bradley-Whitman
, M. A. Lovell

Producción científica: Article › revisión exhaustiva

175 Citas (Scopus)

Resumen

The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p<. 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p<. 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.

Idioma original	English
Páginas (desde-hasta)	486-495
Número de páginas	10
Publicación	Mechanisms of Ageing and Development
Volumen	134
N.º	10
DOI	https://doi.org/10.1016/j.mad.2013.08.005
Estado	Published - oct 2013

Nota bibliográfica

Funding Information:
This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank the UK-ADC Clinical, Neuropathology and Biostatistics Cores for tissue procurement and neuropathologic data. The authors also thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.

Financiación

This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank the UK-ADC Clinical, Neuropathology and Biostatistics Cores for tissue procurement and neuropathologic data. The authors also thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.

Financiadores	Número del financiador
National Institutes of Health (NIH)	5P01-AG05119
National Institute on Aging	P30AG028383

ASJC Scopus subject areas

Aging
Developmental Biology

Acceder al documento

10.1016/j.mad.2013.08.005

Otros archivos y enlaces

Citar esto

@article{802b7699b0374870b0e38740cb477f9f,

title = "Epigenetic changes in the progression of Alzheimer's disease",

abstract = "The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p<. 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p<. 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.",

keywords = "5-Hydroxymethylcytosine, 5-Methylcytosine, Alzheimer's disease, Preclinical Alzheimer's disease",

author = "Bradley-Whitman, \{M. A.\} and Lovell, \{M. A.\}",

note = "Funding Information: This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank the UK-ADC Clinical, Neuropathology and Biostatistics Cores for tissue procurement and neuropathologic data. The authors also thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.",

year = "2013",

month = oct,

doi = "10.1016/j.mad.2013.08.005",

language = "English",

volume = "134",

pages = "486--495",

number = "10",

}

TY - JOUR

T1 - Epigenetic changes in the progression of Alzheimer's disease

AU - Bradley-Whitman, M. A.

AU - Lovell, M. A.

N1 - Funding Information: This research was supported by NIH grants 5P01-AG05119 and P30-AG028383 . The authors thank the UK-ADC Clinical, Neuropathology and Biostatistics Cores for tissue procurement and neuropathologic data. The authors also thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.

PY - 2013/10

Y1 - 2013/10

N2 - The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p<. 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p<. 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.

AB - The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer's disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p<. 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p<. 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.

KW - 5-Hydroxymethylcytosine

KW - 5-Methylcytosine

KW - Alzheimer's disease

KW - Preclinical Alzheimer's disease

UR - https://www.scopus.com/pages/publications/84888133742

UR - https://www.scopus.com/pages/publications/84888133742#tab=citedBy

U2 - 10.1016/j.mad.2013.08.005

DO - 10.1016/j.mad.2013.08.005

M3 - Article

C2 - 24012631

AN - SCOPUS:84888133742

SN - 0047-6374

VL - 134

SP - 486

EP - 495

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

IS - 10

ER -

Epigenetic changes in the progression of Alzheimer's disease

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto