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Record W4294762973 · doi:10.1007/s00401-022-02454-z

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

2022· review· en· W4294762973 on OpenAlexaff
Iris E. Jansen, Sven J. van der Lee, Duber Gomez‐Fonseca, Itziar de Rojas, Carolina Dalmasso, Benjamin Grenier‐Boley, Anna Zettergren, Aniket Mishra, Muhammad Ali, Víctor Andrade, Céline Bellenguez, Luca Kleineidam, Fahri Küçükali, Yun Ju Sung, Niccoló Tesi, Eleonora M. Vromen, Douglas P. Wightman, Daniel Alcolea, Montserrat Alegret, Ignacio Álvarez, Philippe Amouyel, Lavinia Athanasiu, Shahram Bahrami, Henri Bailly, Olivia Belbin, Sverre Bergh, Lars Bertram, Geert Jan Biessels, Kaj Blennow, Rafael Blesa, Merçé Boada, Anne Boland, Katharina Büerger, Ángel Carracedo, Laura Cervera‐Carles, Geneviève Chêne, Jurgen A.H.R. Claassen, Stéphanie Debette, Jean‐François Deleuze, Peter Paul De Deyn, Janine Diehl‐Schmid, Srdjan Djurovic, Oriol Dols‐Icardo, Carole Dufouil, Emmanuelle Duron, Emrah Düzel, Tormod Fladby, Juan Fortea, Lutz Frölich, Pablo García‐González, María García‐Martínez, Ina Giegling, Oliver Goldhardt, Johan Gobom, Timo Grimmer, Annakaisa Haapasalo, Harald Hampel, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann‐Heimbach, Seppo Helisalmi, Michael T. Heneka, Isabel Hernández, Sanna‐Kaisa Herukka, Henne Holstege, Jonas Alexander Jarholm, Silke Kern, Anne‐Brita Knapskog, Anne M. Koivisto, Johannes Kornhuber, Teemu Kuulasmaa, Carmen Lage, Christoph Laske, Ville Leinonen, Piotr Lewczuk, Alberto Lleó, Adolfo López de Munain, Sara López‐García, Wolfgang Maier, Marta Marquié, Merel O. Mol, Laura Montrreal, Fermín Moreno, Sonia Moreno–Grau, Gaël Nicolas, Markus M. Nöthen, Adelina Orellana, Lene Pålhaugen, Janne M. Papma, Florence Pasquier, Robert Perneczky, Oliver Peters, Yolande A.L. Pijnenburg, Julius Popp, Daniëlle Posthuma, Ana Pozueta, Josef Priller, Raquel Puerta, Inés Quintela, Inez Ramakers, Eloy Rodríguez‐Rodríguez, Dan Rujescu, Ingvild Saltvedt, Pascual Sánchez‐Juan, Philip Scheltens, Norbert Scherbaum, Matthias Schmid, Anja Schneider, Geir Selbæk, Per Selnes, Alexey Shadrin, Ingmar Skoog, Hilkka Soininen, Lluís Tárraga, Stefan Teipel, Betty M. Tijms, Magda Tsolaki, Christine Van Broeckhoven, Jasper Van Dongen, John C. van Swieten, Rik Vandenberghe, Jean‐Sébastien Vidal, Pieter Jelle Visser, Jonathan Vogelgsang, Margda Wærn, Michael Wagner, Jens Wiltfang, Mandy Melissa Jane Wittens, Henrik Zetterberg, Miren Zulaica, Cornelia M. van Duijn, Maria Bjerke, Sebastiaan Engelborghs, Frank Jessen, Charlotte E. Teunissen, Pau Pástor, Mikko Hiltunen, Martin Ingelsson, Ole A. Andreassen, Jordi Clarimón, Kristel Sleegers, Agustı́n Ruiz, Alfredo Ramı́rez, Carlos Cruchaga, Jean‐Charles Lambert, Wiesje M. van der Flier

Bibliographic record

VenueActa Neuropathologica · 2022
Typereview
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsOntario Brain InstituteUniversity of TorontoUniversity Health Network
FundersNational Institute on AgingNational Institutes of HealthFondation pour la Recherche sur AlzheimerJulius ClinicalCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasServierInstituto de Salud Carlos IIISiemens HealthineersStichting DioraphteHersenstichtingUniversiteit AntwerpenOryzon GenomicsVetenskapsrådetEisaiFonds Wetenschappelijk OnderzoekNovo NordiskEuropean Regional Development FundBundesministerium für Bildung und ForschungAcademy of FinlandAmsterdam NeuroscienceZonMwNederlandse Organisatie voor Wetenschappelijk OnderzoekGrifolsAgence Nationale de la RechercheH. Lundbeck A/SSunovionDeutsches Zentrum für Neurodegenerative ErkrankungenDeutsche ForschungsgemeinschaftEuropean Federation of Pharmaceutical Industries and AssociationsEU Joint Programme – Neurodegenerative Disease ResearchDanoneEuropean CommissionVlaamse regeringEsteve PharmaceuticalsAlzheimer NederlandPfizerBiogenHealth~HollandHope Center for Neurological DisordersEli Lilly and Company
KeywordsCerebrospinal fluidBiobankPathogenesisEtiologyAlzheimer's diseaseLocus (genetics)Genome-wide association studyDementiaDiseaseBiologyApolipoprotein EMedicinePathologyBioinformaticsGeneticsGeneSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Meta-epidemiology (broad), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.481
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0060.012
Bibliometrics0.0010.002
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0060.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.263
GPT teacher head0.397
Teacher spread0.134 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designMeta-analysis
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations138
Published2022
Admission routes1
Has abstractyes

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