| Title: |
Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers |
| Authors: |
Jansen, I.E.; van der Lee, S.J.; Gomez-Fonseca, D.; de Rojas, I.; Dalmasso, M.C.; Grenier-Boley, B.; Zettergren, A.; Mishra, A.; Ali, M.; Andrade, V.; Bellenguez, C.; Kleineidam, L.; Küçükali, F.; Sung, Y.J.; Tesí, N.; Vromen, E.M.; Wightman, D.P.; Alcolea, D.; Alegret, M.; Alvarez, I.; Amouyel, P.; Athanasiu, L.; Bahrami, S.; Bailly, H.; Belbin, O.; Bergh, S.; Bertram, L.; Biessels, G.J.; Blennow, K.; Blesa, R.; Boada, M.; Boland, A.; Buerger, K.; Carracedo Álvarez, Ángel; Cervera-Carles, L.; Chene, G.; Claassen, J.A.H.R.; Debette, S.; Deleuze, J.-F.; de Deyn, P.P.; Diehl-Schmid, J.; Djurovic, S.; Dols-Icardo, O.; Dufouil, C.; Duron, E.; Düzel, E.; Fladby, T.; Fortea, J.; Frölich, L.; García-González, P.; Garcia-Martinez, M.; Giegling, I.; Goldhardt, O.; Gobom, J.; Grimmer, T.; Haapasalo, A.; Hampel, H.; Hanon, O.; Hausner, L.; Heilmann-Heimbach, S.; Helisalmi, S.; Heneka, M.T.; Hernández, I.; Herukka, S.-K.; Holstege, H.; Jarholm, J.; Kern, S.; Knapskog, A.-B.; Koivisto, A.M.; Kornhuber, J.; Kuulasmaa, T.; Lage, C.; Laske, C.; Leinonen, V.; Lewczuk, P.; Lleó, A.; de Munain, A.L.; Lopez-Garcia, S.; Maier, W.; Marquié, M.; Mol, M.O.; Montrreal, L.; Moreno, F.; Moreno-Grau, S.; Nicolas, G.; Nöthen, M.M.; Orellana, A.; Pålhaugen, L.; Papma, J.M.; Pasquier, F.; Perneczky, R.; Peters, O.; Pijnenburg, Y.A.L.; Popp, J.; Posthuma, D.; Pozueta, A.; Priller, J.; Puerta, R.; Quintela García, Inés; Ramakers, I.; Rodriguez-Rodriguez, E.; Rujescu, D.; Saltvedt, I.; Sanchez-Juan, P.; Scheltens, P.; Scherbaum, N.; Schmid, M.; Schneider, A.; Selbæk, G.; Selnes, P.; Shadrin, A.; Skoog, I.; Soininen, H.; Tárraga, L.; Teipel, S.; Tijms, B.; Tsolaki, M.; Van Broeckhoven, C.; Van Dongen, J.; van Swieten, J.C.; Vandenberghe, R.; Vidal, J.-S.; Visser, P.J.; Vogelgsang, J.; Waern, M.; Wagner, M.; Wiltfang, J.; Wittens, M.M.J.; Zetterberg, H.; Zulaica, M.; van Duijn, C.M.; Bjerke, M.; Engelborghs, S.; Jessen, F.; Teunissen, C.E.; Pastor, P.; Hiltunen, M.; Ingelsson, M.; Andreassen, O.A.; Clarimón, J.; Sleegers, K.; Ruiz, A.; Ramirez, A.; Cruchaga, C.; Lambert, J.-C.; van der Flier, W. |
| Publication Year: |
2022 |
| Subject Terms: |
FPGMX; AS Santiago; IDIS |
| Description: |
Amyloid-beta 42 (A?42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A?42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A?42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume. ; This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Programme, Neurodegenerative Disease Research (JPND). Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). Part of the work described in this study was carried out in the context of the Parelsnoer Institute (PSI). PSI was part of and funded by the Dutch Federation of University Medical Centers and has received initial funding from the Dutch Government (from ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
EU Joint Programme, Neurodegenerative Disease Research (JPND); Stichting Alzheimer Nederland; Stichting VUmc fonds; Stichting Dioraphte; JPco-fuND (ZonMW project) [FP-829-029, 733051061]; Dutch Federation of University Medical Centers; Dutch Government; JPND EADB grant (German Federal Ministry of Education and Research (BMBF)) [01ED1619A]; German Research Foundation (DFG) [RA 1971/6-1, RA1971/7-1, RA 1971/8-1]; Grifols SA; Fundacion bancaria 'La Caixa'; Fundacio ACE; CIBERNED; European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED project [115975, 115985]; European Union/EFPIA Innovative Medicines Initiative Joint undertaking MOPEAD project [115975, 115985]; ISCIII (Instituto de Salud Carlos III)-Subdireccion General de Evaluacion; Fondo Europeo de Desarrollo Regional (FEDER-'Una manera de hacer Europa'); PFIS Contratos Predoctorales de Formacion en Investigacion en Salud [FI20/00215]; NIH [P30AG066444, P01AG003991]; Hope Center for Neurological Disorders; Neurogenomics and Informatics Center; Alzheimer Research Foundation (SAO-FRA); Research Foundation Flanders (FWO); University of Antwerp Research Fund; BOF DOCPRO fellowship of the University of Antwerp Research Fund; Instituto de Salud Carlos III (Fondo de Investigacion Sanitario) [PI08/0139, PI12/02288, PI16/01652, PI20/01011]; JPND [DEMTEST PI11/03028]; Siemens Healthineers; Valdecilla Biobank [PT17/0015/0019]; EU Joint Programme-Neurodegenerative Disease Research [301220]; Academy of Finland [338182]; German Center for Neurodegenerative Diseases (DZNE); German Federal Ministry of Education and Research (BMBF) [01G10102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 04GI0434, 01GI0711]; ZonMW [73305095007]; HealthHolland, Topsector Life Sciences Health [LSHM20106]; Hersenstichting; Edwin Bouw Fonds; Gieskes-Strijbisfonds; NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology [NWO: 024.004.012]; Swedish Alzheimer Foundation [AF-939988, AF-930582, AF-646061, AF-741361, AF-842471, AF-737641, AF-939825, AF-742881]; Dementia Foundation [2020-04-13, 2021-0417]; Swedish government [ALF 716681, ALFGBG-81392, ALF GBG-771071, ALFGBG-715986]; Swedish Research Council [2017-009151, 1267, 825-2012-5041, 2013-8717, 2015-02830, 2017-00639, 2019-01096, 2019-02075, 2016-01590, 2018-02532]; Swedish Research Council for Health, Working Life and Welfare [2001-2646, 2001-2835, 2001-2849, 2003-0234, 2004-0150, 20050762, 2006-0020, 2008-1229, 2008-1210, 2012-1138, 2004-0145, 2006-0596, 2008-1111, 2010-0870, 2013-1202, 2013-2300, 20132496]; Swedish Brain Power, Hjarnfonden, Sweden [FO2016-0214, FO2018-0214, FO2019-0163]; Alzheimer's Association Zenith Award [ZEN-01-3151]; Alzheimer's Association Stephanie B. Overstreet Scholars [IIRG-00-2159]; Alzheimer's Association [IIRG-03-6168, IIRG-09-131338]; Bank of Sweden Tercentenary Foundation; BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology [024.004.012]; European Research Council advanced grant [ERC-2018-AdG GWAS2FUNC 834057]; European Research Council [681712]; Swedish State Support for Clinical Research [ALFGBG-720931]; Alzheimer Drug Discovery Foundation (ADDF), USA [2018092016862]; European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie [860197]; UK Dementia Research Institute at UCL; Hjarnfonden, Sweden [FO2017-0243]; European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]; National Institute of Health (NIH), USA [1R01AG06839801]; Alzheimer's Association 2021 Zenith Award [ZEN-21848495]; National Institutes of Health [R01AG044546, R01AG064877, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501, R01AG064614]; Chuck Zuckerberg Initiative (CZI); Department of Neurology at Washington University School of Medicine; Department of Psychiatry at Washington University School of Medicine; [PI13/02434]; [PI16/01861]; [PI17/01474]; [PI19/01240]; [PI19/01301]; Academy of Finland (AKA) [301220] Funding Source: Academy of Finland (AKA); National Institute on Aging [U01AG058922] Funding Source: NIH RePORTER; https://link.springer.com/content/pdf/10.1007%2Fs00401-022-02454-z.pdf;https://link.springer.com/content/pdf/10.1007/s00401-022-02454-z.pdf; https://portalcientifico.sergas.gal/documentos/63389a0a250f6f2135360dd2; https://hdl.handle.net/20.500.11940/20673; 63389a0a250f6f2135360dd2 |
| DOI: |
10.1007/s00401-022-02454-z |
| Availability: |
https://hdl.handle.net/20.500.11940/20673; https://portalcientifico.sergas.gal/documentos/63389a0a250f6f2135360dd2; https://doi.org/10.1007/s00401-022-02454-z |
| Rights: |
Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0/ ; openAccess |
| Accession Number: |
edsbas.36EC86C |
| Database: |
BASE |