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Cited by 132Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

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

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Jansen, Iris E., van der Lee, Sven J., Gomez-Fonseca, Duber, de Rojas, Itziar, Dalmasso, Maria Carolina, Grenier-Boley, Benjamin, Zettergren, Anna, Mishra, Aniket +140 more·2022·Acta Neuropathologica
DOI 10.1007/s00401-022-02454-zPMC PMC9547780

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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.

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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, Á., 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., EADB consortium, 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, 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., The GR@ACE study group, 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.
Affiliations
  • Amsterdam Neuroscience (NL)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • University of Gothenburg (SE)
  • Université de Bordeaux (FR)
  • Washington University in St. Louis (US)
  • Inserm (FR)
  • University of Bonn (DE)
  • University of Antwerp (BE)
  • Universitat Autònoma de Barcelona (ES)
  • Instituto de Salud Carlos III (ES)
  • University of Oslo (NO)
  • Université Paris Cité (FR)
  • Innlandet Hospital Trust (NO)
  • University of Lübeck (DE)
  • University Medical Center Utrecht (NL)
  • Sahlgrenska University Hospital (SE)
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
  • Universidade de Santiago de Compostela (ES)
  • Radboud University Medical Center (NL)
  • Oslo University Hospital (NO)
  • German Center for Neurodegenerative Diseases (DE)
  • Central Institute of Mental Health (DE)
  • Medical University of Vienna (AT)
  • TUM Klinikum (DE)
  • University of Eastern Finland (FI)
  • Sorbonne Université (FR)
  • Akershus University Hospital (NO)
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Universidad de Cantabria (ES)
  • Medical University of Białystok (PL)
  • Erasmus MC (NL)
  • Universitat Internacional de Catalunya (ES)
  • University of Zurich (CH)
  • Maastricht University (NL)
  • Norwegian University of Science and Technology (NO)
  • University of Duisburg-Essen (DE)
  • University Hospital Bonn (DE)
  • Aristotle University of Thessaloniki (GR)
  • Karolinska Institutet (SE)
  • Harvard University (US)
  • Vrije Universiteit Brussel (BE)
  • University of Cologne (DE)
  • Uppsala University (SE)
Corresponding author
Jansen, Iris E.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2022-09-06
Volume
144
Issue
5
Pages
821-842
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-022-02454-z
PMC
PMC9547780
OpenAlex
W4294762973
Cited by
132
References
82
Citations by year
2026: 30 · 2025: 38 · 2024: 37 · 2023: 23 · 2022: 4
FWCI
16.55
Type
journal article
Language
en
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Funders
EU Joint Programme – Neurodegenerative Disease Research (European Alzheimer DNA BioBank, EADB)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
Alzheimer's disease, cerebrospinal fluid biomarkers, amyloid-beta 42, phosphorylated tau, genetic susceptibility loci, complement receptor 1, BIN1, apolipoprotein E, lateral ventricular volume
MeSH terms
Alzheimer Disease, Apolipoproteins E, Humans, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Cell Cycle Proteins

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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