TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
Year: 2021
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. METHODS: We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. RESULTS: We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. DISCUSSION: Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.12330
Authors: Shengjun Hong, Valerija Dobricic, Olena Ohlei, Isabelle Bos, Stephanie J. B. Vos, Dmitry Prokopenko, Betty M. Tijms, Ulf Andreasson, Kaj Blennow, Rik Vandenberghe, Silvy Gabel, Philip Scheltens, Charlotte E. Teunissen, Sebastiaan Engelborghs, Giovanni Frisoni, Olivier Blin, Jill C. Richardson, Regis Bordet, Alzheimer's Disease Neuroimaging Initiative (ADNI), Alberto Lleó, Daniel Alcolea, Julius Popp, Christopher Clark, Gwendoline Peyratout, Pablo Martinez‐Lage, Mikel Tainta, Richard J. B. Dobson, Cristina Legido‐Quigley, Kristel Sleegers, Christine Van Broeckhoven, Rudolph E. Tanzi, Mara ten Kate, Michael Wittig, Andre Franke, Christina M. Lill, Frederik Barkhof, Simon Lovestone, Johannes Streffer, Henrik Zetterberg, Pieter Jelle Visser, Lars Bertram
Institutions: University of Lübeck, Maastricht University, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, Massachusetts General Hospital, Sahlgrenska University Hospital, University of Gothenburg, Universitair Ziekenhuis Leuven, KU Leuven, Vrije Universiteit Brussel, University of Antwerp, Universitair Ziekenhuis Brussel, Institute Born-Bunge, University of Geneva, Centro San Giovanni di Dio Fatebenefratelli, Aix-Marseille Université, GlaxoSmithKline (United Kingdom), Inserm, Université de Lille, Centre Hospitalier Universitaire de Lille, Hospital de Sant Pau, Biomedical Research Networking Center on Neurodegenerative Diseases, Alzheimer’s Disease Neuroimaging Initiative, Centro de Investigación Biomédica en Red, Centre Hospitalier Universitaire Vaudois, Psychiatrische Universitätsklinik Zürich, Fundacion CITA Alzheimer, University of London, King's College London, South London and Maudsley NHS Foundation Trust, National Institute for Health and Care Research, UCL Biomedical Research Centre, Health Data Research UK, NIHR Maudsley Biomedical Research Centre, University College London, Steno Diabetes Center Copenhagen, VIB-UAntwerp Center for Molecular Neurology, Christian-Albrechts-Universität zu Kiel, Imperial College London, University of Oxford, UCB Pharma (Belgium), UK Dementia Research Institute, UCL Queen Square Institute of Neurology, Karolinska Institutet, University of Oslo
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Funders: Alzheimer's Drug Discovery Foundation, Alzheimer's Disease Neuroimaging Initiative, Cure Alzheimer's Fund, EU Joint Programme – Neurodegenerative Disease Research, European Federation of Pharmaceutical Industries and Associations, Steno Diabetes Center Copenhagen, European Commission, National Research Foundation, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, ZonMw, Hjärnfonden, Vetenskapsrådet, Universiteit Antwerpen, Innovative Medicines Initiative, Vlaamse regering, National Institutes of Health, Canadian Institutes of Health Research, Medical Research Council, National Institute on Aging, H2020 European Research Council, Cilag
Awards: G104586243, G1073258374, G1253720191, G1323383031, G1551449788, G1563972089, G160417252, G1732308444, G1901141725, G2082095200, G2107972360, G2108271864, G2109279595, G2144614533, G2385484910, The Alzheimer biomarker toolbox – use in pathogenic studies, diagnostics and theragnostics, G2841269746, G2871734582, G3027168043, G308275008, G313301595, G3207356259, Real world Outcomes across the AD spectrum for better care: Multimodal data Access Platform - Sofia ref.: 116020, Macrophage migration inhibitory factor and neuroinflammation in early Alzheimer’s Disease, G393177772, G3998764592, G4075158157, G4181470480, G4404751248, G4428953086, G4703319937, G4760961572, G5111822078, Flächensparen beim Verkehr, G56684467, G5702163051, Alzheimer's Disease Neuroimaging Initiative, G6069138294, G607220997, G6142763750, G6168044258, G6382720711, G6492936739, Pathways to Alzheimer's disease, G712881263, G7143958211, G7198253607, G7376789991, G7498027273, G7896934920, G791739130, European Medical Information Framework, What determines amyloid beta aggregation and toxicity in Alzheimer’s disease?, G958583170, G96521508
OpenAlex ID: W3160827273