Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Jansen RE, Van Der Lee SJ, Gomez-Fonseca D, De Rojas I, Dalmasso MC, Grenier-Boley B, Zettergren A, Mishra A, Ali M, Andrade V, Bellenguez C, Kleineidam L, Kucukali F, Sung YJ, Tesi N, Vromen EM, Wightman DP, Alcolea D, Alegret M, Alvarez I, Amouyel P, Athanasiu L, Bahrami S, Bailly H, Belbin O, Bergh S, Bertram L, Biessels GJ, Blennow K, Blesa R, Boada M, Boland A, Buerger K, Carracedo A, Cervera-Carles L, Chene G, Claassen JAHR, Debette S, Deleuze JF, De Deyn PP, Diehl-Schmid J, Djurovic S, Dols-Icardo O, Dufouil C, Duron E, Duezel E, Fladby T, Fortea J, Froelich L, Garcia-Gonzalez 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 MT, Hernandez I, Herukka SK, Holstege H, Jarholm J, Kern S, Knapskog AB, Koivisto AM, Kornhuber J, Kuulasmaa T, Lage C, Laske C, Leinonen V, Lewczuk P, Lleo A, De Munain AL, Lopez-Garcia S, Maier W, Marquie M, Mol MO, Montrreal L, Moreno F, Moreno-Grau S, Nicolas G, Nothen MM, Orellana A, Palhaugen L, Papma JM, Pasquier F, Perneczky R, Peters O, Pijnenburg YAL, Popp J, Posthuma D, Pozueta A, Priller J, Puerta R, Quintela I, Ramakers I, Rodriguez-Rodriguez E, Rujescu D, Saltvedt I, Sanchez-Juan P, Scheltens P, Scherbaum N, Schmid M, Schneider A, Selbaek G, Selnes P, Shadrin A, Skoog I, Soininen H, Tarraga L, Teipel S, Tijms B, Tsolaki M, Van Broeckhoven C, Van Dongen J, Van Swieten JC, Vandenberghe R, Vidal JS, Visser PJ, Vogelgsang J, Waern M, Wagner M, Wiltfang J, Wittens MMJ, Zetterberg H, Zulaica M, Van Duijn CM, Bjerke M, Engelborghs S, Jessen F, Teunissen CE, Pastor P, Hiltunen M, Ingelsson M, Andreassen OA, Clarimon J, Sleegers K, Ruiz A, Ramirez A, Cruchaga C, Lambert JC, Van Der Flier W (2022)

Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1007/s00401-022-02454-z

Abstract

Amyloid-beta 42 (A beta 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 beta 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 beta 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.

Authors with CRIS profile

Involved external institutions

École Polytechnique - Université Paris-Saclay France (FR) Technische Universität München (TUM) Germany (DE) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Instituto de Salud Carlos III (Institute of Health Carlos III, ISCIII) Spain (ES) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Germany (DE) University of Oslo Norway (NO) Medizinische Fakultät Mannheim der Universität Heidelberg Germany (DE) Universitat Internacional de Catalunya Spain (ES) Universidad de Cantabria (UC) Spain (ES) University of Eastern Finland Finland (FI) University of Paris 4 - Paris-Sorbonne / Université paris IV Paris-Sorbonne France (FR) Université de Paris France (FR) Universitätsklinikum Bonn Germany (DE) Institut national de physique nucléaire et de physique des particules (IN2P3) France (FR) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Vestfold Hospital / Sykehuset i Vestfold Norway (NO) University of Gothenburg / Göteborgs universitet Sweden (SE) Erasmus University Medical Center (MC) Netherlands (NL) University of Antwerp / Universiteit Antwerpen Belgium (BE) Universität zu Köln Germany (DE) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Hospital Universitari Germans Trias i Pujol Spain (ES) Uppsala University Sweden (SE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) Washington University in St. Louis United States (USA) (US) LILLE 1 University - Science and Technology France (FR) Universitätsklinikum Göttingen Germany (DE) MútuaTerrassa University Hospital / Hospital Universitario MútuaTerrassa / Hospital Universitari MútuaTerrassa Spain (ES) Innlandet Hospital / Sykehuset Innlandet Norway (NO) Universität zu Lübeck Germany (DE) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) University of Santiago de Compostela / Universidad de Santiago de Compostela (USC) Spain (ES) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) Medizinische Universität Wien Austria (AT) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) Akershus University Hospital / Akershus universitetssykehus (Ahus) Norway (NO) Maastricht University Netherlands (NL) Université de Caen Basse-Normandie France (FR) Psychiatrische Universitätsklinik Zürich Switzerland (CH) NTNU Trondheim - Norwegian University of Science and Technology Norway (NO) Alzheimer Center Reina Sofia Foundation Spain (ES) Universität Duisburg-Essen (UDE) Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Aristotle University of Thessaloniki Greece (GR)

How to cite

APA:

Jansen, R.E., Van Der Lee, S.J., Gomez-Fonseca, D., De Rojas, I., Dalmasso, M.C., Grenier-Boley, B.,... Van Der Flier, W. (2022). Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. Acta Neuropathologica. https://doi.org/10.1007/s00401-022-02454-z

MLA:

Jansen, Ris E., et al. "Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers." Acta Neuropathologica (2022).

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