Association of peripheral blood DNA methylation level with Alzheimer's disease progression.
Alzheimer’s disease
DMP
DMR
EWAS
Epigenetics
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
15 10 2021
15 10 2021
Historique:
received:
05
04
2021
accepted:
29
09
2021
entrez:
16
10
2021
pubmed:
17
10
2021
medline:
19
2
2022
Statut:
epublish
Résumé
Identifying biomarkers associated with Alzheimer's disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites and AD pathology and diagnosis. Here, we report relationships between peripheral blood DNA methylation profiles measured using Infinium® MethylationEPIC BeadChip and AD progression in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The rate of cognitive decline from initial DNA sampling visit to subsequent visits was estimated by the slopes of the modified Preclinical Alzheimer Cognitive Composite (mPACC; mPACC Candidate CpG sites and regions in peripheral blood were identified as associated with the rate of cognitive decline in participants in the ADNI cohort. While we did not identify a single CpG site with sufficient clinical utility to be used by itself due to the observed effect size, a biosignature composed of DNA methylation changes may have utility as a prognostic biomarker for AD progression.
Sections du résumé
BACKGROUND
Identifying biomarkers associated with Alzheimer's disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites and AD pathology and diagnosis. Here, we report relationships between peripheral blood DNA methylation profiles measured using Infinium® MethylationEPIC BeadChip and AD progression in participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
RESULTS
The rate of cognitive decline from initial DNA sampling visit to subsequent visits was estimated by the slopes of the modified Preclinical Alzheimer Cognitive Composite (mPACC; mPACC
CONCLUSION
Candidate CpG sites and regions in peripheral blood were identified as associated with the rate of cognitive decline in participants in the ADNI cohort. While we did not identify a single CpG site with sufficient clinical utility to be used by itself due to the observed effect size, a biosignature composed of DNA methylation changes may have utility as a prognostic biomarker for AD progression.
Identifiants
pubmed: 34654479
doi: 10.1186/s13148-021-01179-2
pii: 10.1186/s13148-021-01179-2
pmc: PMC8518178
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
191Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : DoD Alzheimer's Disease Neuroimaging Initiative (US)
ID : W81XWH-12-2-0012
Informations de copyright
© 2021. The Author(s).
Références
Mol Brain. 2018 Apr 10;11(1):20
pubmed: 29631601
Dement Geriatr Cogn Disord. 2006;21(1):40-3
pubmed: 16254429
Epigenomics. 2018 May;10(5):585-595
pubmed: 29692214
JAMA Neurol. 2014 Aug;71(8):961-70
pubmed: 24886908
Arch Clin Neuropsychol. 2014 Dec;29(8):767-75
pubmed: 25352087
Genesis. 2000 Feb;26(2):118-20
pubmed: 10686603
Clin Epigenetics. 2020 Oct 17;12(1):149
pubmed: 33069246
Nat Neurosci. 2014 Sep;17(9):1164-70
pubmed: 25129077
BMC Neurol. 2019 Oct 31;19(1):264
pubmed: 31672138
Clin Epigenetics. 2020 Feb 3;12(1):20
pubmed: 32014019
Alzheimers Dement. 2019 Jan;15(1):106-152
pubmed: 30321505
Nat Commun. 2021 Jun 10;12(1):3517
pubmed: 34112773
Nat Med. 2018 May;24(5):598-603
pubmed: 29736028
Immunol Cell Biol. 2020 Jan;98(1):28-41
pubmed: 31654430
J Mol Neurosci. 2020 Oct;70(10):1589-1597
pubmed: 32472396
Neuroimage. 2015 Jan 1;104:398-412
pubmed: 25312773
Development. 2003 Nov;130(21):5191-201
pubmed: 12954718
Antioxidants (Basel). 2019 May 05;8(5):
pubmed: 31060341
Bioinformatics. 2019 Jun 1;35(11):1958-1959
pubmed: 30346483
Int J Neurosci. 2021 Jan 18;:1-12
pubmed: 33401985
Epigenetics Chromatin. 2015 Jan 27;8:6
pubmed: 25972926
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Alzheimers Dement. 2013 Feb;9(1 Suppl):S39-44
pubmed: 22858530
Neurol Genet. 2019 Jun 24;5(4):e342
pubmed: 31403079
Gastroenterology. 2019 Jun;156(8):2254-2265.e3
pubmed: 30779925
Clin Exp Med. 2018 Feb;18(1):1-14
pubmed: 28752221
Intelligence. 2011 Jul;39(4):222-232
pubmed: 21789028
Alzheimers Res Ther. 2014 Jul 03;6(4):37
pubmed: 25024750
Ann Clin Transl Neurol. 2020 Jul;7(7):1225-1239
pubmed: 32634865
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Front Immunol. 2019 Jun 04;10:1170
pubmed: 31214167
Lancet Neurol. 2013 Feb;12(2):207-16
pubmed: 23332364
Front Aging Neurosci. 2017 Dec 12;9:413
pubmed: 29311901
Alzheimers Dement (N Y). 2021 May 25;7(1):e12179
pubmed: 34095440
Neurogastroenterol Motil. 2012 Oct;24(10):e497-508
pubmed: 22897442
N Engl J Med. 2010 Jan 28;362(4):329-44
pubmed: 20107219
Neuron. 2002 Apr 25;34(3):371-85
pubmed: 11988169
PLoS One. 2020 Jul 27;15(7):e0235663
pubmed: 32716914
J Cent Nerv Syst Dis. 2020 Feb 29;12:1179573520907397
pubmed: 32165850
PLoS One. 2015 Dec 04;10(12):e0143563
pubmed: 26636579
Bioinformatics. 2012 Nov 15;28(22):2986-8
pubmed: 22954632
Alzheimers Dement. 2013 Feb;9(1 Suppl):S45-55
pubmed: 22658286
Alzheimers Dement (N Y). 2019 Aug 07;5:364-373
pubmed: 31440579
Genome Biol. 2017 Jan 27;18(1):19
pubmed: 28129774
J Clin Psychopharmacol. 2018 Oct;38(5):513-519
pubmed: 30124583
Front Aging Neurosci. 2014 Apr 16;6:75
pubmed: 24795628
JAMA. 2017 Jun 13;317(22):2305-2316
pubmed: 28609533
Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361
pubmed: 27899662
Epigenetics Chromatin. 2018 Jul 25;11(1):41
pubmed: 30045751
J Neuropathol Exp Neurol. 2020 May 1;79(5):484-492
pubmed: 32296844
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
Epigenetics. 2016 Aug 2;11(8):563-78
pubmed: 27245352
Clin Epigenetics. 2020 Jun 15;12(1):84
pubmed: 32539856
Clin Epigenetics. 2019 Nov 27;11(1):164
pubmed: 31775875
J Alzheimers Dis. 2018;66(3):927-934
pubmed: 30372681
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
J Neural Transm (Vienna). 2009 Aug;116(8):995-1005
pubmed: 19291360
Nat Neurosci. 2014 Sep;17(9):1156-63
pubmed: 25129075
Development. 2003 Dec;130(23):5663-79
pubmed: 14522873
PLoS One. 2016 Jun 20;11(6):e0157776
pubmed: 27322064
Acta Biomed. 2020 Mar 19;91(1):157-160
pubmed: 32191675
Alzheimers Dement. 2018 Dec;14(12):1580-1588
pubmed: 29550519
Bioinformatics. 2016 Jan 15;32(2):286-8
pubmed: 26424855
Arch Neurol. 2009 May;66(5):638-45
pubmed: 19433664
Circulation. 2017 Oct 17;136(16):1528-1544
pubmed: 28838933
Neurosci Biobehav Rev. 2016 Apr;63:1-28
pubmed: 26814961
J Alzheimers Dis. 2007 Dec;12(4):365-75
pubmed: 18198423
Cell Rep. 2020 Jun 30;31(13):107843
pubmed: 32610143
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
Neurobiol Aging. 2020 Nov;95:26-45
pubmed: 32745807
PLoS One. 2017 Aug 3;12(8):e0182098
pubmed: 28771542
Hippocampus. 2014 Apr;24(4):363-8
pubmed: 24436131
Neuron. 1999 Apr;22(4):677-91
pubmed: 10230789
Int J Mol Sci. 2020 May 05;21(9):
pubmed: 32380758
PLoS One. 2016 Jan 07;11(1):e0146449
pubmed: 26742120
Alzheimers Dement (N Y). 2019 Sep 25;5:483-491
pubmed: 31650004