Alzheimer's disease-associated (hydroxy)methylomic changes in the brain and blood.

5-Methylcytosine / analogs & derivatives Age of Onset Aged Aged, 80 and over Alzheimer Disease / genetics Brain Chemistry DNA Methylation Disease Progression Epigenesis, Genetic Female Humans Intracellular Signaling Peptides and Proteins / genetics Male Oxytocin / genetics Receptors, Nicotinic / genetics Temporal Lobe / chemistry
Alzheimer’s disease Blood Brain DNA hydroxymethylation DNA methylation Epigenetics Middle temporal gyrus

Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
27 11 2019
Historique:
received: 08 04 2019
accepted: 26 09 2019
entrez: 29 11 2019
pubmed: 30 11 2019
medline: 28 7 2020
Statut: epublish

Résumé

Late-onset Alzheimer's disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD. We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (- 3.76% 5mC, p The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.

Sections du résumé

BACKGROUND
Late-onset Alzheimer's disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD.
RESULTS
We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (- 3.76% 5mC, p
CONCLUSIONS
The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.

Identifiants

DOI: 10.1186/s13148-019-0755-5 PMID: 31775875 PMC: PMC6880587
pubmed: 31775875
doi: 10.1186/s13148-019-0755-5
pii: 10.1186/s13148-019-0755-5
pmc: PMC6880587
doi:

Substances chimiques

CHRNB1 protein, human 0
Intracellular Signaling Peptides and Proteins 0
RHBDF2 protein, human 0
Receptors, Nicotinic 0
5-hydroxymethylcytosine 1123-95-1
Oxytocin 50-56-6
5-Methylcytosine 6R795CQT4H

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

164

Subventions

Organisme : Medical Research Council
ID : MR/N027973/1
Pays : United Kingdom

Références

Nat Rev Drug Discov. 2009 Apr;8(4):286-95
pubmed: 19337271
Epigenetics Chromatin. 2013 Aug 06;6(1):26
pubmed: 23919675
J Alzheimers Dis. 2019;70(3):691-713
pubmed: 31256118
Bioinformatics. 2006 Sep 15;22(18):2291-7
pubmed: 16844706
Brain Res. 1993 Apr 23;609(1-2):154-8
pubmed: 8508299
Bioinformatics. 2003 Nov 1;19(16):2155-7
pubmed: 14594725
Hum Mol Genet. 2014 Apr 1;23(7):1947-56
pubmed: 24242183
Alzheimers Dement. 2017 Jun;13(6):674-688
pubmed: 28089213
FASEB J. 2011 Jun;25(6):1934-42
pubmed: 21368103
Acta Neuropathol. 2016 Apr;131(4):481-504
pubmed: 26689922
Epigenetics. 2013 Feb;8(2):203-9
pubmed: 23314698
J Biol Chem. 2017 Mar 17;292(11):4533-4543
pubmed: 28115522
J Med Dent Sci. 2003 Sep;50(3):225-9
pubmed: 15074360
Curr Alzheimer Res. 2017;14(4):377-392
pubmed: 27697062
Am J Med Genet B Neuropsychiatr Genet. 2013 Dec;162B(8):789-99
pubmed: 24038819
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Neurology. 1987 Jun;37(6):1001-3
pubmed: 3587615
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Neurobiol Aging. 1992 Mar-Apr;13(2):261-5
pubmed: 1522943
Nat Neurosci. 2014 Sep;17(9):1164-70
pubmed: 25129077
Clin Epigenetics. 2019 Mar 21;11(1):52
pubmed: 30898171
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Science. 2009 May 15;324(5929):929-30
pubmed: 19372393
Science. 2012 Jan 13;335(6065):225-8
pubmed: 22246777
Neuropathology. 2015 Aug;35(4):354-89
pubmed: 25619230
J Alzheimers Dis. 2015;44(4):1203-12
pubmed: 25524954
Trends Biochem Sci. 2013 Oct;38(10):480-4
pubmed: 23932479
Endocr Rev. 2008 Dec;29(7):865-97
pubmed: 18824526
Cell Death Dis. 2014 Aug 21;5:e1382
pubmed: 25144717
Clin Neuropathol. 1985 May-Jun;4(3):127-34
pubmed: 3160517
Nat Rev Genet. 2011 Jan;12(1):56-68
pubmed: 21164525
Cell Death Dis. 2016 Jan 14;7:e2040
pubmed: 26775695
BMC Syst Biol. 2010 Oct 06;4:136
pubmed: 20925940
J Alzheimers Dis. 2017;56(1):157-166
pubmed: 27911312
Acta Neuropathol. 2013 Oct;126(4):479-97
pubmed: 24052108
Mol Metab. 2017 Dec;6(12):1610-1615
pubmed: 29157601
Int J Biochem Cell Biol. 2009 May;41(5):990-3
pubmed: 18723111
Bioorg Med Chem. 2016 Sep 15;24(18):4254-4262
pubmed: 27460669
Science. 2016 May 6;352(6286):712-716
pubmed: 27033548
Genomics. 2006 Aug;88(2):163-72
pubmed: 16714093
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Neurobiol Aging. 2014 Jun;35(6):1334-44
pubmed: 24387984
Prog Neurobiol. 2015 Aug;131:21-64
pubmed: 26072273
Dement Geriatr Cogn Disord. 2007;24(4):307-16
pubmed: 17848793
Neurobiol Aging. 2014 Nov;35(11):2436-2443
pubmed: 24958192
Bioinformatics. 2012 Nov 15;28(22):2986-8
pubmed: 22954632
Genome Biol. 2017 Jan 27;18(1):19
pubmed: 28129774
Alzheimer Dis Assoc Disord. 2014 Jul-Sep;28(3):226-33
pubmed: 24731980
Genomics. 2014 Nov;104(5):376-82
pubmed: 25205305
Peptides. 2014 Dec;62:15-20
pubmed: 25278490
J Hum Genet. 2009 Jul;54(7):386-91
pubmed: 19461657
Genome Res. 2012 Mar;22(3):467-77
pubmed: 22106369
Neurobiol Dis. 2014 Feb;62:273-85
pubmed: 24141019
Front Cell Neurosci. 2017 Mar 09;11:63
pubmed: 28337127
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):E3816-23
pubmed: 27325757
Neuron. 2014 Nov 5;84(3):608-22
pubmed: 25442939
Epigenetics Chromatin. 2018 Jul 25;11(1):41
pubmed: 30045751
Nat Neurosci. 2014 Sep;17(9):1156-63
pubmed: 25129075
Clin Epigenetics. 2018 Jun 1;10:73
pubmed: 29881472
Am J Psychiatry. 1982 Sep;139(9):1136-9
pubmed: 7114305
Neurology. 1984 Jul;34(7):939-44
pubmed: 6610841
Neurobiol Aging. 2013 Sep;34(9):2091-9
pubmed: 23582657
Cell Tissue Bank. 2008 Sep;9(3):229-45
pubmed: 18347928
Psychoneuroendocrinology. 2013 Sep;38(9):1883-94
pubmed: 23856187
Genome Med. 2016 Jan 19;8(1):5
pubmed: 26803900
Psychoneuroendocrinology. 2017 Mar;77:165-174
pubmed: 28064086
BMC Genomics. 2013 May 01;14:293
pubmed: 23631413
Oncotarget. 2016 Apr 12;7(15):19089-98
pubmed: 26943045
J Biol Chem. 2014 May 2;289(18):12680-92
pubmed: 24627487

Auteurs

Roy Lardenoije (R)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075, Göttingen, Germany.

Janou A Y Roubroeks (JAY)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
University of Exeter Medical School, University of Exeter, Exeter, UK.

Ehsan Pishva (E)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
University of Exeter Medical School, University of Exeter, Exeter, UK.

Markus Leber (M)

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937, Cologne, Germany.

Holger Wagner (H)

Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127, Bonn, Germany.

Artemis Iatrou (A)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.

Adam R Smith (AR)

University of Exeter Medical School, University of Exeter, Exeter, UK.

Rebecca G Smith (RG)

University of Exeter Medical School, University of Exeter, Exeter, UK.

Lars M T Eijssen (LMT)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
Department of Bioinformatics-BiGCaT, Maastricht University, Maastricht, The Netherlands.

Luca Kleineidam (L)

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937, Cologne, Germany.
Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.

Amit Kawalia (A)

Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127, Bonn, Germany.

Per Hoffmann (P)

Institute of Human Genetics, University of Bonn, 53127, Bonn, Germany.
Department of Genomics, Life & Brain Center, University of Bonn, 53127, Bonn, Germany.
Division of Medical Genetics, University Hospital and Department of Biomedicine, University of Basel, CH-4058, Basel, Switzerland.

Tobias Luck (T)

Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, 04103, Leipzig, Germany.

Steffi Riedel-Heller (S)

Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, 04103, Leipzig, Germany.

Frank Jessen (F)

German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.
Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937, Cologne, Germany.

Wolfgang Maier (W)

Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.

Michael Wagner (M)

Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127, Bonn, Germany.
German Center for Neurodegenerative Diseases (DZNE), 53127, Bonn, Germany.

René Hurlemann (R)

Department of Psychiatry and Division of Medical Psychology, University of Bonn, 53105, Bonn, Germany.

Gunter Kenis (G)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.

Muhammad Ali (M)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Antonio Del Sol (A)

Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Moscow Institute of Physics and Technology, Dolgoprudny, Moscow, Russian Federation.
CIC bioGUNE, Bizkaia Technology Park, 801 Building, 48160, Derio, Spain.
IKERBASQUE, Basque Foundation for Science, Dolgoprudny, Bilbao, Spain.

Diego Mastroeni (D)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.
L.J. Roberts Center for Alzheimer's Research Banner Sun Health Research Institute, Sun City, AZ, USA.
Biodesign Institute, Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA.

Elaine Delvaux (E)

L.J. Roberts Center for Alzheimer's Research Banner Sun Health Research Institute, Sun City, AZ, USA.
Biodesign Institute, Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA.

Paul D Coleman (PD)

L.J. Roberts Center for Alzheimer's Research Banner Sun Health Research Institute, Sun City, AZ, USA.
Biodesign Institute, Neurodegenerative Disease Research Center, Arizona State University, Tempe, AZ, USA.

Jonathan Mill (J)

University of Exeter Medical School, University of Exeter, Exeter, UK.
Institute of Psychiatry, King's College London, London, UK.

Bart P F Rutten (BPF)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands.

Katie Lunnon (K)

University of Exeter Medical School, University of Exeter, Exeter, UK.

Alfredo Ramirez (A)

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, 50937, Cologne, Germany.
Department of Neurodegeneration and Gerontopsychiatry, University of Bonn, 53127, Bonn, Germany.

Daniël L A van den Hove (DLA)

School for Mental Health and Neuroscience (MHeNS), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200, MD, Maastricht, the Netherlands. d.vandenhove@maastrichtuniversity.nl.
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. d.vandenhove@maastrichtuniversity.nl.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Pyrimidines › Pyrimidinones › Cytosine › 5-Méthyl-cytosine › Alzheimer's disease-associated...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs âges › Âge de début › Alzheimer's disease-associated...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Alzheimer's disease-associated...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Alzheimer's disease-associated...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Alzheimer's disease-associated...
questionsmedicales.fr › Métabolisme › Chimie du cerveau › Alzheimer's disease-associated...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Alzheimer's disease-associated...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Alzheimer's disease-associated...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Alzheimer's disease-associated...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Alzheimer's disease-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Alzheimer's disease-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones hypophysaires › Hormones post-hypophysaires › Ocytocine › Alzheimer's disease-associated...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs cholinergiques › Récepteurs nicotiniques › Alzheimer's disease-associated...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe temporal › Alzheimer's disease-associated...