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

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, Á.; Cervera-Carles, L.; Chene, G.; Claassen, JAHR; 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, 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.; 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, MMJ; 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.

doi:10.1007/s00401-022-02454-z

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

Details

Download: 36066633_BIB_2F3F6E6D5A81.pdf (1437.81 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_2F3F6E6D5A81

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Acta neuropathologica

Author(s)

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 Á., Cervera-Carles L., Chene G., Claassen JAHR, 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 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., 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 MMJ, 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.

Working group(s)

EADB consortium, GR@ACE study group

ISSN

1432-0533 (Electronic)

ISSN-L

0001-6322

Publication state

Published

Issued date

11/2022

Peer-reviewed

Oui

Volume

144

Number

Pages

821-842

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish

Abstract

Amyloid-beta 42 (Aβ42) 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 Aβ42 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 Aβ42 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.

Keywords

Alzheimer Disease/pathology, Amyloid beta-Peptides/cerebrospinal fluid, Apolipoproteins E/genetics, Biomarkers/cerebrospinal fluid, Cell Cycle Proteins, Humans, Peptide Fragments/cerebrospinal fluid, tau Proteins/cerebrospinal fluid, tau Proteins/genetics, Alzheimer’s disease, Amyloid-beta, Cerebrospinal fluid, GWAS, Tau

URN

urn:nbn:ch:serval-BIB_2F3F6E6D5A817

OAI-PMH

oai:serval.unil.ch:BIB_2F3F6E6D5A81

DOI

10.1007/s00401-022-02454-z

Pubmed

36066633

Web of science

000850433700001

Open Access

Yes