ArticlemedRxiv : the preprint server for health sciences2025
Epigenome-wide association study of cerebrospinal fluid-based biomarkers of Alzheimer's disease in cognitively normal individuals.
Anke Hüls, Jiaqi Liu, Chaini Konwar, Karen N Conneely, Allan I Levey, James J Lah, Aliza P Wingo, Thomas S Wingo
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
8 authors.
Anke HülsDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA, 30322.ORCID 0000-0002-6005-417X Jiaqi LiuDepartment of Psychiatry, University of California, Davis, Sacramento, CA USA, 95816.
Chaini KonwarCentre for Molecular Medicine and Therapeutics, The University of British Columbia, Vancouver BC V5Z 4H4, Canada.
Karen N ConneelyDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA USA, 95816.
Allan I LeveyGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA USA, 30322.
James J LahGoizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA USA, 30322.
Aliza P WingoDivision of Mental Health, Northern California VA, Sacramento, CA USA, 95816.
Thomas S WingoDepartment of Neurology, University of California, Davis, Sacramento, CA USA, 95816.
Funding
The Emory Healthy Brain Study: Discovering Predictive Biomarkers for Alzheimer's DiseaseR01AG070937 · NIA · EMORY UNIVERSITY · PI LAH, JAMES J · 2021 to 2025
$35.2MThe Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI Jonathan David Glass · 2020 to 2026
$29.0MUC Davis Alzheimer's Disease Research CenterP30AG072972 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Rachel A Whitmer · 2021 to 2026
$25.2MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MSupplement to AMP-AD Brain Proteomic Network Enhancement, Validation and Translation into CSF BiomarkersU01AG061357 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I, SEYFRIED, NICHOLAS THOMAS · 2018 to 2022
$9.1MDiscovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4MIMPACT-ADRD: Investigating the Multi-omics Perturbations Associated with Complex Environmental Toxicants and their Contribution to Alzheimer's Disease and Related DementiasU01AG088425 · NIA · EMORY UNIVERSITY · PI Anke Huels, Donghai Liang · 2024 to 2026
$6.8MThe brain multi-omic approach to identify key molecular drivers of neuropsychiatric symptoms in Alzheimer's dementiaR01AG072120 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Aliza Pham Wingo, Thomas Spurgeon Wingo · 2022 to 2026
$4.3MUnderstanding the molecular mechanisms of Depression and Psychological Well-being in Alzheimer's diseaseR01AG056533 · NIA · EMORY UNIVERSITY · PI WINGO, ALIZA PHAM, WINGO, THOMAS SPURGEON · 2017 to 2021
$3.9MIntegrative genomic, transcriptomic, and proteomic analyses to investigate sex-specific differences in Alzheimer's DiseaseR01AG075827 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Aliza Pham Wingo, Thomas Spurgeon Wingo · 2022 to 2026
$3.7MAir pollution and early signs of dementiaR01AG079170 · NIA · EMORY UNIVERSITY · PI Anke Huels, Thomas Spurgeon Wingo · 2022 to 2026
$3.6MAir pollution, the blood and brain metabolome and their effects on Alzheimer's disease and related dementiasR01AG087250 · NIA · EMORY UNIVERSITY · PI Anke Huels, Donghai Liang · 2024 to 2026
$2.3MBLRD VA I01 BX003853BLRD VA I01 BX005686BLRD VA IK4 BX005219NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG072972NIA NIH HHS R01 AG056533NIA NIH HHS R01 AG070937NIA NIH HHS R01 AG072120NIA NIH HHS R01 AG075827NIA NIH HHS R01 AG079170NIA NIH HHS R01 AG087250NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG061356NIA NIH HHS U01 AG061357NIA NIH HHS U01 AG088425
6 · The paper itselfAbstract
introductionCerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are reliable predictors of future AD risk. We investigated whether pre-clinical changes in AD CSF biomarkers are reflected in blood DNA methylation (DNAm) levels in cognitively normal participants.
methodsWe profiled blood-based DNAm with the EPIC array in participants without a diagnosis of cognitive impairment in the Emory Healthy Brain Study (EHBS; N=495) and ADNI (N=122). Their CSF Aβ42, tTau, and pTau levels were quantified using Elecsys immunoassays. We conducted epigenome-wide association studies to assess associations between DNAm and CSF biomarkers of AD.
resultsIn EHBS, no loci were Bonferroni-significant after adjusting for confounding factors. In ADNI, two loci were significant, but they were not replicated in EHBS. There was little agreement between the top loci from EHBS and ADNI. DISCUSSION: Our study showed little evidence of an association between differential blood-based DNAm and pre-clinical AD CSF biomarkers.
Indexed as
Alzheimer’s disease (AD)amyloidbiomarkerbloodcerebrospinal fluid (CSF)DNA methylationepigeneticsepigenome-wide association study (EWAS)
Identifiers
PMID39974053
PMCPMC11838696
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