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DNA methylation differences associated with peripheral biomarkers in the EMIF‐AD cohort
Author(s) -
Smith Rebecca G.,
Bos Isabelle,
Vos Stephanie J.B.,
Verhey Frans R.J.,
Scheltens Philip,
Engelborghs Sebastiaan,
Frisoni Giovanni B.,
Blin Olivier,
Richardson Jill,
Bordet Régis,
Tsolaki Magda,
Popp Julius,
MartinezLage Pablo,
Lleó Alberto,
Johannsen Peter,
Freund Yvonne,
Frölich Lutz,
Vandenberghe Rik,
Lovestone Simon,
Streffer Johannes,
Andreasson Ulf,
Blennow Kaj,
Visser Pieter Jelle,
Zetterberg Henrik,
Bertram Lars,
Lun Katie
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045853
Subject(s) - biomarker , dna methylation , epigenetics , cpg site , neurogranin , cohort , oncology , methylation , medicine , bioinformatics , biology , dna , genetics , phosphorylation , gene , gene expression , protein kinase c
Background Alzheimer’s disease is associated with increases in amyloid β and hyperphosphorylated tau which is thought to occur decades before the onset of clinical symptoms, leading to cell loss and inhibition. Finding biomarkers to detect these changes before neuronal loss and therefore permanent damage has occurred is integral. Current biomarkers using cerebrospinal fluid (CSF) measures and positron‐emission tomography (PET) imaging are invasive or expensive to perform. In this study we use the European Medical Information Framework Alzheimer’s disease (EMIF‐AD) cohort to looks for blood related epigenetic (DNA methylation) changes which relate to CSF and existing peripheral biomarkers. Method Whole blood samples from EMIF‐AD were accessed for DNA methylation on Illumina EPIC arrays. We assessed DNA methylation levels in 886 individuals with > 10 central and local biomarker measures, including amyloid, tau, neurogranin and YKL‐40. We also performed regional analysis to look for regions of significant DNA methylation change and identified specific pathways that show methylomic changes in association with specific biomarkers. Result We identified epigenome‐wide significant probes associated with many of our biomarker measures including most notably central amyloid β‐42, amyloid β‐40/42 ratio, neurogranin and YKL‐40 CSF levels as well as with local phosphorylated tau and total tau measurements. We also are able to use collections of CpG sites to create classifiers that predict high levels of CSF biomarkers. Conclusion In the future, identified sites and collections of sites could be used as a proxy for other biomarker measures due to the less invasive and less expensive nature of blood collection DNA methylation analysis. We are currently undertaking further analysis of this cohort using imaging and clinical measures.