DOI: 10.1002/alz.080072 ISSN: 1552-5260

Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer’s disease in the EMIF‐AD Multimodal Biomarker Discovery study

Rebecca G. Smith, Jennifer L Imm, Valerija Dobricic, Yasmine Sommerer, Isabelle Bos, Stephanie J. B. Vos, Frans R.J. Verhey, Philip Scheltens, Sebastiaan Engelborgs, Giovanni B Frisoni, Olivier Blin, Jill C Richardson, Régis Bordet, Magda Tsolaki, Julius Popp, Pablo Martinez‐Lage, Alberto Lleo, Peter Johannsen, Yvonne Freund‐Levi, Frölich Lutz, Rik Vandenberghe, Michael Wittig, Andre Frank, Simon Lovestone, Johannes Streffer, Ulf Andreasson, Kaj Blennow, Pieter Jelle Visser, Henrik Zetterberg, Lars Bertram, Katie Lunnon
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



The aim of this study was to identify DNA methylation signatures that were associated with 15 CSF biomarker measures of Alzheimer’s disease (AD) or neurodegeneration.


We profiled DNA methylation in 886 blood samples from the EMIF‐AD study using the Illumina EPIC array, identifying differentially methylated loci, and regions consisting of multiple adjacent differentially methylated sites.


We identified Bonferroni‐significant differences in DNA methylation with respect to CSF t‐tau Z‐score (five loci), Aβ42 levels (one loci), YKL‐40 levels (six loci) and NFL (seven loci). Significant differentially methylated regions were identified in 13 of the 15 analyses, with overlapping regions featuring in multiple CSF measures(MX2, RHOH, ANKMY1, ZFP57) analyses, which was unsurprising given the high correlation between measures. Interestingly, we identified several regions that overlapped between the tau and amyloid (ZBTB22), tau and NFL (S100A13), NFL and neurogranin (SORD), and neurogranin and amyloid (STRA6) regional analyses.


In this blood‐based epigenome‐wide association study of AD‐relevant CSF biomarkers we identified several interesting genomic loci and regions.

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