TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
Por:
Hong, SJ, Dobricic, V, Ohlei, O, Bos, I, Vos, SJB, Prokopenko, D, Tijms, BM, Andreasson, U, Blennow, K, Vandenberghe, R, Gabel, S, Scheltens, P, Teunissen, CE, Engelborghs, S, Frisoni, G, Blin, O, Richardson, JC, Bordet, R, Lleo, A, Alcolea, D, Popp, J, Clark, C, Peyratout, G, Martinez-Lage, P, Tainta, M, Dobson, RJB, Legido-Quigley, C, Sleegers, K, Van Broeckhoven, C, Tanzi, RE, ten Kate, M, Wittig, M, Franke, A, Lill, CM, Barkhof, F, Lovestone, S, Streffer, J, Zetterberg, H, Visser, PJ, Bertram, L, Neuroimaging Initiative
Publicada:
1 oct 2021
Ahead of Print:
1 may 2021
Resumen:
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.
Filiaciones:
Hong, SJ:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Ratzeburger Allee 160,Haus V50, D-23562 Lubeck, Germany
Dobricic, V:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Ratzeburger Allee 160,Haus V50, D-23562 Lubeck, Germany
Ohlei, O:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Ratzeburger Allee 160,Haus V50, D-23562 Lubeck, Germany
Bos, I:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Amsterdam UMC, Amsterdam, Netherlands
Vos, SJB:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Amsterdam UMC, Amsterdam, Netherlands
Prokopenko, D:
Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Boston, MA 02114 USA
Massachusetts Gen Hosp, Dept Neurol, McCance Ctr Brain Hlth, Boston, MA 02114 USA
Tijms, BM:
Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Amsterdam UMC, Amsterdam, Netherlands
Andreasson, U:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Vandenberghe, R:
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Univ Hosp Leuven, Neurol Serv, Leuven, Belgium
Gabel, S:
Katholieke Univ Leuven, Dept Neurosci, Lab Cognit Neurol, Leuven, Belgium
Scheltens, P:
Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Amsterdam UMC, Amsterdam, Netherlands
Teunissen, CE:
Vrije Univ, Dept Clin Chem, Neurochem Lab, Amsterdam Univ,Med Ctr, Amsterdam, Netherlands
Engelborghs, S:
Univ Antwerp, Inst Born Bunge, Dept Biomed Sci, Antwerp, Belgium
UZ Brussel, Dept Neurol, Brussels, Belgium
UZ Brussel, Ctr Neurosci, Brussels, Belgium
Vrije Univ Brussel VUB, Brussels, Belgium
Frisoni, G:
Univ Geneva, Geneva, Switzerland
IRCCS Ist Ctr San Giovanni Dio Fatebenefratell, Brescia, Italy
Blin, O:
AIX Marseille Univ, AP HM, INS, Marseille, France
Richardson, JC:
GlaxoSmithKline R&D, Neurosci Therapeut Area, Stevenage, Herts, England
Bordet, R:
Univ Lille, CHU Lille, INSERM, Lille, France
Lleo, A:
Hosp Sant Pau, Memory Unit, Neurol Dept, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Alcolea, D:
Hosp Sant Pau, Memory Unit, Neurol Dept, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Popp, J:
Univ Hosp Psychiat Zurich, Dept Geriatr Psychiat, Ctr Gerontopsychiat Med, Zurich, Switzerland
Univ Hosp Lausanne, Dept Psychiat, Old Age Psychiat, Lausanne, Switzerland
Clark, C:
Univ Hosp Psychiat Zurich, Dept Geriatr Psychiat, Ctr Gerontopsychiat Med, Zurich, Switzerland
Peyratout, G:
Univ Hosp Lausanne, Dept Psychiat, Old Age Psychiat, Lausanne, Switzerland
Martinez-Lage, P:
CITA Alzheimer Fdn, Dept Neurol, Ctr Res & Adv Therapies, San Sebastian, Spain
Tainta, M:
CITA Alzheimer Fdn, Dept Neurol, Ctr Res & Adv Therapies, San Sebastian, Spain
Dobson, RJB:
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Biostat & Hlth Informat, London, England
Kings Coll London, NIHR BioResource Ctr Maudsley, NIHRMaudsley Biomed Res Ctr BRC, South London & Maudsley NHS Fdn Trust SLaM, London, England
Kings Coll London, Inst Psychiat Psychol & Neurosci IoPPN, London, England
UCL, Hlth Data Res UK London, London, England
UCL, Inst Hlth Informat, London, England
UCL, Natl Inst Hlth Res, Univ Coll London Hosp, Biomed Res Ctr, London, England
Legido-Quigley, C:
Steno Diabet Ctr, Copenhagen, Denmark
Kings Coll London, Inst Pharmaceut Sci, London, England
Sleegers, K:
VIB, Neurodegenerat Brain Dis Grp, Ctr Mol Neurol, Antwerp, Belgium
Univ Antwerp, Dept Biomed Sci, Antwerp, Belgium
Van Broeckhoven, C:
VIB, Neurodegenerat Brain Dis Grp, Ctr Mol Neurol, Antwerp, Belgium
Univ Antwerp, Dept Biomed Sci, Antwerp, Belgium
Tanzi, RE:
Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Unit, Boston, MA 02114 USA
Massachusetts Gen Hosp, Dept Neurol, McCance Ctr Brain Hlth, Boston, MA 02114 USA
ten Kate, M:
Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Alzheimer Ctr, Amsterdam, Netherlands
Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Neurol, Amsterdam, Netherlands
Univ Amsterdam, Med Ctr, Amsterdam Neurosci, Dept Radiol & Nucl Med, Amsterdam, Netherlands
Wittig, M:
Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany
Franke, A:
Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany
Lill, CM:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Ratzeburger Allee 160,Haus V50, D-23562 Lubeck, Germany
Barkhof, F:
UCL, Inst Neurol & Healthcare Engn, London, England
Lovestone, S:
Univ Oxford, Dept Psychiat, Oxford, England
Janssen Cilag, Beerse, Belgium
Streffer, J:
Univ Antwerp, Inst Born Bunge, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
UCB Biopharma SPRL, Translat Med Neurosci, Braine Lalleud, Belgium
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England
UCL, UK Dementia Res Inst, London, England
Visser, PJ:
Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, Maastricht, Netherlands
Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Dept Neurol, Amsterdam Neurosci,Amsterdam UMC, Amsterdam, Netherlands
Karolinska Instutet, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden
Bertram, L:
Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Ratzeburger Allee 160,Haus V50, D-23562 Lubeck, Germany
Univ Oslo, Dept Psychol, Oslo, Norway
Imperial Coll, Sch Publ Hlth, Ageing Epidemiol Res Unit, London, England.
Green Published, hybrid, Green Submitted
|