Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study
Abstract INTRODUCTION We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration. METHODS We assessed DNA methylation in 885 blood samples from the...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 2024
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| In: |
Alzheimer's and dementia
Year: 2024, Volume: 20, Issue: 10, Pages: 6722-6739 |
| ISSN: | 1552-5279 |
| DOI: | 10.1002/alz.14098 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/alz.14098 Verlag, kostenfrei, Volltext: http://alz.journals.onlinelibrary.wiley.com/doi/10.1002/alz.14098 
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| Author Notes: | Rebecca G. Smith, Ehsan Pishva, Morteza Kouhsar, Jennifer Imm, Valerija Dobricic, Peter Johannsen, Michael Wittig, Andre Franke, Rik Vandenberghe, Jolien Schaeverbeke, Yvonne Freund-Levi, Lutz Frölich, Philip Scheltens, Charlotte E. Teunissen, Giovanni Frisoni, Olivier Blin, Jill C. Richardson, Régis Bordet, Sebastiaan Engelborghs, Ellen de Roeck, Pablo Martinez-Lage, Miren Altuna, Mikel Tainta, Alberto Lleó, Isabel Sala, Julius Popp, Gwendoline Peyratout, Laura Winchester, Alejo Nevado-Holgado, Frans Verhey, Magda Tsolaki, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Stephanie J.B. Vos, Simon Lovestone, Pieter Jelle Visser, Lars Bertram, Katie Lunnon |
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| 245 | 1 | 0 | |a Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study |c Rebecca G. Smith, Ehsan Pishva, Morteza Kouhsar, Jennifer Imm, Valerija Dobricic, Peter Johannsen, Michael Wittig, Andre Franke, Rik Vandenberghe, Jolien Schaeverbeke, Yvonne Freund-Levi, Lutz Frölich, Philip Scheltens, Charlotte E. Teunissen, Giovanni Frisoni, Olivier Blin, Jill C. Richardson, Régis Bordet, Sebastiaan Engelborghs, Ellen de Roeck, Pablo Martinez-Lage, Miren Altuna, Mikel Tainta, Alberto Lleó, Isabel Sala, Julius Popp, Gwendoline Peyratout, Laura Winchester, Alejo Nevado-Holgado, Frans Verhey, Magda Tsolaki, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johannes Streffer, Stephanie J.B. Vos, Simon Lovestone, Pieter Jelle Visser, Lars Bertram, Katie Lunnon |
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| 520 | |a Abstract INTRODUCTION We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration. METHODS We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF-AD) study using the EPIC array. RESULTS We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development. DISCUSSION We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain. Highlights Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)?relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels. | ||
| 650 | 4 | |a Alzheimer's disease (AD) | |
| 650 | 4 | |a amyloid | |
| 650 | 4 | |a biomarker | |
| 650 | 4 | |a blood | |
| 650 | 4 | |a cerebrospinal fluid (CSF) | |
| 650 | 4 | |a DNA methylation | |
| 650 | 4 | |a epigenetics | |
| 650 | 4 | |a epigenome-wide association study (EWAS) | |
| 650 | 4 | |a genome-wide association study (GWAS) | |
| 650 | 4 | |a methylation quantitative trait loci (mQTL) | |
| 650 | 4 | |a mild cognitive impairment (MCI) | |
| 650 | 4 | |a neurofilament light (NfL) | |
| 650 | 4 | |a protein quantitative trait loci (pQTL) | |
| 650 | 4 | |a tau | |
| 650 | 4 | |a YKL-40 | |
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| 700 | 1 | |a Bertram, Lars |e VerfasserIn |4 aut | |
| 700 | 1 | |a Lunnon, Katie |e VerfasserIn |4 aut | |
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