TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
Hong, Shengjun (Lübeck Interdisciplinary Platform for Genome Analytics (LIGA). University of Lübeck)
Dobricic, Valerija (Lübeck Interdisciplinary Platform for Genome Analytics (LIGA). University of Lübeck)
Ohlei, Olena (Lübeck Interdisciplinary Platform for Genome Analytics (LIGA). University of Lübeck)
Bos, Isabelle (Alzheimer Center Amsterdam. Department of Neurology. Amsterdam Neuroscience. Vrije Universiteit Amsterdam)
Vos, Stephanie J.B. (Alzheimer Center Amsterdam. Department of Neurology. Amsterdam Neuroscience. Vrije Universiteit Amsterdam)
Prokopenko, Dimitry (Massachusetts General Hospital (Boston))
Tijms, Betty M. (Vrije Universiteit Amsterdam)
Andreasson, Ulf (Sahlgrenska University Hospital (Suècia))
Blennow, Kaj (Sahlgrenska University Hospital (Suècia))
Vandenberghe, Rik (University Hospitals Leuven (Bèlgica))
Gabel, Silvy (KU Leuven. Department of Neurosciences)
Scheltens, Philip (Vrije Universiteit Amsterdam)
Teunissen, Charlotte E. (Amsterdam University Medical Centers (AUMC))
Engelborghs, Sebastiaan (Vrije Universiteit Brussel)
Frisoni, Giovanni B. (IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli)
Blin, Olivier (AIX Marseille University. INS. Ap-hm)
Richardson, Jill C. (Neurosciences Therapeutic Area. GlaxoSmithKline R&D)
Bordet, Régis (Inserm. CHU Lille. University of Lille)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Popp, Julius (Lausanne University Hospital)
Clark, Christopher (University Hospital of Psychiatry Zurich)
Peyratout, Gwendoline (University Hospital of Lausanne. Department of Psychiatry)
Martinez-Lage, Pablo (Department of Neurology. Center for Research and Advanced Therapies. CITA-Alzheimer Foundation)
Tainta, Mikel (Department of Neurology. Center for Research and Advanced Therapies. CITA-Alzheimer Foundation)
Dobson, Richard J.B. (University College London. Hospitals Biomedical Research Centre)
Legido-Quigley, Cristina (King's College London)
Sleegers, Kristel (University of Antwerp. Institute Born-Bunge)
Van Broeckhoven, Christine (University of Antwerp)
Tanzi, Rudolph E. (Massachusetts General Hospital (Boston))
ten Kate, Mara (Amsterdam UMC. University Medical Center)
Wittig, Michael (Christian-Albrechts-University of Kiel. Institute of Clinical Molecular Biology)
Franke, Andre (Christian-Albrechts-University of Kiel. Institute of Clinical Molecular Biology)
Lill, Christina M. (Imperial College. School of Public Health)
Barkhof, Frederik (University College London. Institutes of Neurology and Healthcare Engineering)
Lovestone, Simon (University of Oxford. Department of Psychiatry)
Streffer, Johannes (Translational Medicine Neuroscience. UCB Biopharma SPRL. Braine l'Alleud)
Zetterberg, Henrik (UCL Institute of Neurology (Regne Unit). UK Dementia Research Institute)
Visser, Pieter J. (Karolinska Instutet. Department of Neurobiology)
Bertram, Lars (University of Oslo. Department of Psychology)

Date:	2021
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.
Grants:	European Commission 115372
Note:	Altres ajuts: German Research Foundation (BE2287/7-1).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer's disease ; Biomarker ; Cerebrospinal fluid ; Chitinase-3-like protein 1 ; Genome-wide association study ; Neurofilament light ; Neurogranin
Published in:	Alzheimer's & Dementia, Vol. 17 Núm. 10 (october 2021) , p. 1628-1640, ISSN 1552-5279

DOI: 10.1002/alz.12330
PMID: 33991015

13 p, 2.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles