Journal Article

DZNE-2022-01541

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.

Jansen, I.Extern* ; 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.DZNE* ; 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. ; Bürger, K.DZNE* ; Carracedo, Á. ; Cervera-Carles, L. ; Chene, G. ; Claassen, J. A. H. R. ; Debette, S. ; Deleuze, J.-F. ; de Deyn, P. P. ; Diehl-Schmid, J.Extern* ; Djurovic, S. ; Dols-Icardo, O. ; Dufouil, C. ; Duron, E. ; Düzel, E.DZNE* ; consortium, E. (Collaboration Author) ; Fladby, T. ; Fortea, J. ; Frölich, L.Extern* ; 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.DZNE* ; 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.DZNE* ; Leinonen, V. ; Lewczuk, P. ; Lleó, A. ; de Munain, A. L. ; Lopez-Garcia, S. ; Maier, W.Extern* ; Marquié, M. ; Mol, M. O. ; Montrreal, L. ; Moreno, F. ; Moreno-Grau, S. ; Nicolas, G. ; Nöthen, M. M.Extern* ; Orellana, A. ; Pålhaugen, L. ; Papma, J. M. ; Pasquier, F. ; Perneczky, R.DZNE* ; Peters, O.DZNE* ; Pijnenburg, Y. A. L. ; Popp, J. ; Posthuma, D. ; Pozueta, A. ; Priller, J.DZNE* ; Puerta, R. ; Quintela, I. ; Ramakers, I. ; Rodriguez-Rodriguez, E. ; Rujescu, D. ; Saltvedt, I. ; Sanchez-Juan, P. ; Scheltens, P. ; Scherbaum, N. ; Schmid, M.Extern* ; Schneider, A.DZNE* ; Selbæk, G. ; Selnes, P. ; Shadrin, A. ; Skoog, I. ; Soininen, H. ; Tárraga, L. ; Teipel, S.DZNE* ; group, G. s. (Collaboration Author) ; 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.DZNE* ; Wiltfang, J.DZNE* ; Wittens, M. M. J. ; Zetterberg, H. ; Zulaica, M. ; van Duijn, C. M. ; Bjerke, M. ; Engelborghs, S. ; Jessen, F.DZNE* ; Teunissen, C. E. ; Pastor, P. ; Hiltunen, M. ; Ingelsson, M. ; Andreassen, O. A.Extern* ; Clarimón, J. ; Sleegers, K. ; Ruiz, A. ; Ramirez, A.DZNE* ; Cruchaga, C. ; Lambert, J.-C. ; van der Flier, W.

2022
Springer Heidelberg

This record in other databases:    

Please use a persistent id in citations: doi:10.1007/s00401-022-02454-z

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.

Keyword(s): Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Apolipoproteins E: genetics (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Cell Cycle Proteins (MeSH) ; Humans (MeSH) ; Peptide Fragments: cerebrospinal fluid (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; tau Proteins: genetics (MeSH) ; Alzheimer’s disease ; Amyloid-beta ; Cerebrospinal fluid ; GWAS ; Tau

Note: CC BY: https://creativecommons.org/licenses/by/4.0/

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Contributing Institute(s):

1. Neuropsychology (AG Wagner)
2. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
3. Clinical Neurophysiology and Memory (AG Düzel)
4. Interventional Trials and Biomarkers in Neurodegenerative Diseases (Biomarker)
5. Parkinson Genetics (AG Gasser)
6. Interdisciplinary Dementia Research (AG Endres)
7. Translational Neuropsychiatry (AG Priller)
8. Translational Dementia Research (Bonn) (AG Schneider)
9. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
10. Clinical Alzheimer’s Disease Research (AG Jessen)
11. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
12. Patient Studies Bonn (Patient Studies Bonn)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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