ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- Impact of zervimesine on the neuroinflammatory biomarker GFAP and related proteomic molecular correlates in plasma of participants from a phase 2 clinical trial in Alzheimer's disease.Alzheimer's research & therapy · 2026Trial
- A new era of genome-wide association studies in the field of Alzheimer's disease and overlapping co-pathologies: lessons learned from a neuropathology-centered approach.Acta neuropathologica · 2026Review
- Shared genetic architecture between Alzheimer's disease and brain morphology.Alzheimer's research & therapy · 2026Article
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A human-derived Bacteroides strain attenuates depressive-like behavior in a rat model of social defeat-induced stress.BMC medicine · 2026Article
- BMAL1-GPX3 axis in the choroid plexus mitigates Aβ pathology in an amyloid mouse model.Journal of neuroinflammation · 2026Article
- Circulating C-reactive protein influences polygenic risk of inflammatory genes expressed in brain endothelia for Alzheimer's disease.Neurobiology of disease · 2026Article
- Proteomic Profiling and Therapeutic Targeting of Oxidative Stress in Autoimmune Encephalitis.Journal of molecular neuroscience : MN · 2025Article
- Cerebrospinal Fluid Metabolomics and Proteomics Integration in Neurological Syndromes.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
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Authors and funding
23 authors.
Daniel J PanyardDepartment of Genetics, Stanford University School of Medicine, Stanford University, Stanford, California, USA.
Lianne M ReusAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Muhammad AliDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Jihua LiuDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Yuetiva K DemingDepartment of Population Health Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Qiongshi LuDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Gwendlyn KollmorgenRoche Diagnostics GmbH, Penzberg, Germany.
Margherita CarboniRoche Diagnostics International Ltd, Rotkreuz, Switzerland.
Norbert WildRoche Diagnostics GmbH, Penzberg, Germany.
Pieter J VisserAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Lars BertramLübeck Interdisciplinary Platform for Genome Analytics, Institutes of Neurogenetics and Cardiogenetics, University of Lübeck, Lübeck, Germany.
Henrik ZetterbergInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Johan GobomInstitute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Dan WesternDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Yun Ju SungDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Cynthia M CarlssonWisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sterling C JohnsonWisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sanjay AsthanaWisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Betty M TijmsAlzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Corinne D EngelmanDepartment of Population Health Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Michael P SnyderDepartment of Genetics, Stanford University School of Medicine, Stanford University, Stanford, California, USA.
Funding
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger · 1985 to 2026
$69.5MWisconsin Registry for Alzheimer's Prevention: Sex Differences in DNA MethylationR01AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Nathaniel Ark Chin, Sterling C Johnson · 2007 to 2026
$35.6MWisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI AMY J. KIND · 2019 to 2026
$34.5MInstitutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2MResearch Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7MThe Longitudinal Course of Neural Function and Amyloid in People At Risk for ADR01AG021155 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sterling C Johnson · 2004 to 2026
$27.0MStatistical Data Enclave CoreP30AG017266 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Michal Engelman · 1999 to 2026
$17.0MWisconsin Alzheimer's Disease Research CenterP50AG033514 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI CHAPPELL, RICHARD J · 2009 to 2018
$16.2MTR&D 2 Metabolic Labels for Ultraplexed Protein Quantification p. 453P41GM108538 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI COON, JOSHUA J · 2016 to 2025
$13.1MDissecting the Genomic Etiology of non-Mendelian Early-Onset Alzheimer Disease and Related PhenotypesR01AG064614 · NIA · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BEECHAM, GARY WAYNE, CRUCHAGA, CARLOS · 2019 to 2023
$11.5MBiology of Aging and Age-Related Diseases Training GrantT32AG000213 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Rozalyn M. Anderson, Sanjay Asthana · 1991 to 2026
$9.9MAD Strategic Fund and the Alzheimer's Association #ADSF-21-831376-CAD Strategic Fund and the Alzheimer's Association #ADSF-21-831377-CAD Strategic Fund and the Alzheimer's Association #ADSF-21-831381-CALF-agreement #ALFGBG-715986ALF-agreement #ALFGBG-965240Alzheimer Drug Discovery Foundation #201809-2016862Alzheimerfonden #AF-930934Alzheimerfonden AF-930934Alzheimer's Association 2021 Zenith Award ZEN-21-848495Alzheimer's Association Research Fellowship 2019-AARF-643973Chan Zuckerberg Initiative (CZI)Clinical and Translational Science Award (CTSA) program through the NIH National Center for Advancing Translational Sciences (NCATS) UL1TR000427EMIF #115372Erling-Persson Family Foundation #EP2019-02European Commission 101034344European Commission 115952European Commission 806999European Research Council #101053962European Union's Horizon 2020European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska'Curie #JPND2021-00694Foundation of Gamla TjänarinnorGenomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's Disease R01AG054047Hjärnfonden #ALZ2022-0006Hjärnfonden #FO2017-0243Hjärnfonden #FO2019-0228Identifying Metabolomic Risk Factors in Plasma and CSF for Alzheimer's Disease R21AG067092Innovative Medicines Inititiative Joint Undertaking under the EMIF #115372Longitudinal Course of Imaging Biomarkers in People at Risk of AD R01AG021155Marie Skłodowska-Curie 860197Memorabel fellowship (ZonMW) 10510022110012National Center for Quantitative Biology of Complex Systems P41GM108538NCATS NIH HHS UL1 TR000427NCATS NIH HHS UL1 TR002373NIA NIH HHS 1RF1AG074007NIA NIH HHS P01 AG003991NIA NIH HHS P01AG003991NIA NIH HHS P30 AG017266NIA NIH HHS P30AG017266NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30AG066444NIA NIH HHS P50 AG033514NIA NIH HHS R01 AG021155NIA NIH HHS R01AG021155NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG037639NIA NIH HHS R01AG037639NIA NIH HHS R01 AG044546NIA NIH HHS R01AG044546NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG064614NIA NIH HHS R01AG064614NIA NIH HHS R01 AG064877NIA NIH HHS R01AG064877NIA NIH HHS R01 AG074007NIA NIH HHS R01AG27161NIA NIH HHS R21 AG067092NIA NIH HHS R21AG067092NIA NIH HHS RF1 AG053303NIA NIH HHS RF1AG053303NIA NIH HHS RF1 AG054047NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS T32 AG000213NIA NIH HHS T32AG000213NIA NIH HHS U01 AG058922NIA NIH HHS U01AG058922NICHD NIH HHS P2C HD047873NIGMS NIH HHS P41 GM108538NIH HHS 1RF1AG074007NIH HHS P01AG003991NIH HHS P30AG066444NIH HHS P41GM108538NIH HHS R01AG044546NIH HHS R01AG054047NIH HHS R01AG064614NIH HHS R01AG064877NIH HHS RF1AG053303NIH HHS RF1AG058501NIH HHS U01AG058922NIH National Center for Advancing Translational Sciences (NCATS) UL1TR000427Olav Thon Foundation #OT2016-101Stiftelsen för Gamla Tjänarinnor #SGT2021-09-ZetterbergSwedish Alzheimer Foundation #AF-930351Swedish Alzheimer Foundation #AF-939721Swedish Alzheimer Foundation #AF-968270Swedish Government and the County CouncilsSwedish Research Council #2017-00915Swedish Research Council #2018-02532Swedish State Support for Clinical Research #ALFGBG-720931UK Dementia Research Institute #UKDRI-1003University of Wisconsin-Madison P2CHD047873White Matter Degeneration: Biomarkers in Preclinical Alzheimer's Disease R01AG037639Wisconsin Alzheimer's Disease Research Center P30AG062715Wisconsin Alzheimer's Disease Research Center P50AG033514Wisconsin Alzheimer's Disease Research Center Grant P30AG062715Wisconsin Alzheimer's Disease Research Center Grant P50AG033514Wisconsin Registry for Alzheimer Prevention: Biomarkers of Preclinical AD R01AG27161ZonMw #733050824736ZonMw #73305095005ZonMW Memorabel 10510022110012ZonMW Memorabel #733050824ZonMW Memorabel grant programma #733050824Zon-MW, NCDC #73305095005Zon-MW, Redefining Alzheimer's disease #733050824736
Abstract
introductionRecent genome-wide association studies (GWAS) have reported a genetic association with Alzheimer's disease (AD) at the TNIP1/GPX3 locus, but the mechanism is unclear.
methodsWe used cerebrospinal fluid (CSF) proteomics data to test (n = 137) and replicate (n = 446) the association of glutathione peroxidase 3 (GPX3) with CSF biomarkers (including amyloid and tau) and the GWAS-implicated variants (rs34294852 and rs871269).
resultsCSF GPX3 levels decreased with amyloid and tau positivity (analysis of variance P = 1.5 × 10 DISCUSSION: These results suggest variants in the TNIP1 locus may affect the oxidative stress response in AD via altered GPX3 levels. HIGHLIGHTS: Cerebrospinal fluid (CSF) glutathione peroxidase 3 (GPX3) levels decreased with amyloid and tau positivity and higher CSF phosphorylated tau. The minor allele of rs34294852 was associated with lower CSF GPX3. levels when also controlling for amyloid and tau category. GPX3 transcript levels in the prefrontal cortex were lower in Alzheimer's disease than controls. rs34294852 is an expression quantitative trait locus for GPX3 in blood, neutrophils, and microglia.
Indexed as
Alzheimer DiseaseGenome-Wide Association StudyGlutathione Peroxidasetau ProteinsAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersDNA-Binding ProteinsFemaleHumansMalePolymorphism, Single NucleotideProteomicsAmyloid beta-PeptidesBiomarkersDNA-Binding ProteinsGlutathione PeroxidaseGPX3 protein, humantau ProteinsTNIP1 protein, humanAlzheimer's diseasegenome‐wide association studiesgenomicsglutathione peroxidase 3proteomics
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