Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study

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Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study

Smith, Rebecca G. (author): Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, Devon, UK

Pishva, Ehsan (author): Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, Devon, UK; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands

Kouhsar, Morteza (author): Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, Devon, UK

Imm, Jennifer (author): Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, Devon, UK

Dobricic, Valerija (author): Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany

Johannsen, Peter (author): Danish Dementia Research Centre, Rigshospitalet, Copenhagen, Denmark

Wittig, Michael (author): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany

Franke, Andre (author): Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany

Vandenberghe, Rik (author): Laboratory for Cognitive Neurology, KU Leuven, Leuven Brain Institute, Leuven, Belgium

Schaeverbeke, Jolien (author): Laboratory for Cognitive Neurology, KU Leuven, Leuven Brain Institute, Leuven, Belgium

Freund-Levi, Yvonne, 1956- (author): Örebro universitet,Institutionen för medicinska vetenskaper,Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, Södertälje Hospital, Södertälje, Sweden

Frölich, Lutz (author): Department of Geriatric Psychiatry, Central Institut of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany

Scheltens, Philip (author): Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands

Teunissen, Charlotte E. (author): Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands

Frisoni, Giovanni (author): Memory center, Geneva University and University Hospitals; AMYPAD consortium, Geneva, Switzerland

Blin, Olivier (author): Aix-Marseille University-CNRS, Marseille, France

Richardson, Jill C. (author): Neuroscience Therapeutic Area, GlaxoSmithKline R&D, Stevenage, Hertfordshire, UK

Bordet, Régis (author): Université de Lille, Lille, Cedex, France

Engelborghs, Sebastiaan (author): Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuroprotection & Neuromodulation (NEUR) Research Group, Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Jette, Brussels, Belgium

de Roeck, Ellen (author): Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

Martinez-Lage, Pablo (author): Center for Research and Advanced Therapies, Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Gipuzkoa, Spain

Altuna, Miren (author): Center for Research and Advanced Therapies, Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Gipuzkoa, Spain

Tainta, Mikel (author): Center for Research and Advanced Therapies, Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Gipuzkoa, Spain

Lleó, Alberto (author): Servicio de Neurología, Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Hospital Sant Pau, Barcelona, Spain

Sala, Isabel (author): Servicio de Neurología, Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Hospital Sant Pau, Barcelona, Spain

Popp, Julius (author): University Hospital of Psychiatry Zürich, University of Zürich, Zürich, Switzerland

Peyratout, Gwendoline (author): Department of Psychiatry, University Hospital of Lausanne (CHUV), Lausanne, Switzerland

Winchester, Laura (author): Department of Psychiatry, University of Oxford, Oxford, UK

Nevado-Holgado, Alejo (author): Department of Psychiatry, University of Oxford, Oxford, UK

Verhey, Frans (author): Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands

Tsolaki, Magda (author): 1st Department of Neurology, School of Medicine, Laboratory of Neurodegenerative Diseases, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, and Alzheimer Hellas, Thessaloniki, Greece

Andreasson, Ulf (author): Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden

Blennow, Kaj (author): Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden; Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France; Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, PR China

Zetterberg, Henrik (author): Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, N.T., Shatin, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA

Streffer, Johannes (author): Translational Medicine Neuroscience, UCB Biopharma SRL, Brussels, Belgium

Vos, Stephanie J. B. (author): Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands

Lovestone, Simon (author): Department of Psychiatry, University Hospital of Lausanne (CHUV), Lausanne, Switzerland; Johnson & Johnson Innovative Medicines, Beerse, Belgium

Visser, Pieter Jelle (author): Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health, Medicine and Life Sciences (FHML), Maastricht University, Maastricht, The Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands

Bertram, Lars (author): Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany

Lunnon, Katie (author): Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, Devon, UK

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2024
2024
English.
In: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279.

Related links:: https://doi.org/10.1...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Alzheimer's disease (AD)
DNA methylation
YKL‐40
amyloid
biomarker
blood
cerebrospinal fluid (CSF)
epigenetics
epigenome‐wide association study (EWAS)
genome‐wide association study (GWAS)
methylation quantitative trait loci (mQTL)
mild cognitive impairment (MCI)
neurofilament light (NfL)
protein quantitative trait loci (pQTL)
tau

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art (subject category)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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