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

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

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).

BibTeX: Download