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Record W2167563852 · doi:10.1093/hmg/ddu372

SUCLG2 identified as both a determinator of CSF Aβ1–42 levels and an attenuator of cognitive decline in Alzheimer's disease

2014· article· en· W2167563852 on OpenAlexfundno aff
Alfredo Ramı́rez, Wiesje M. van der Flier, Christine Herold, David Ramonet, Stefanie Heilmann‐Heimbach, Piotr Lewczuk, Julius Popp, André Lacour, Dmitriy Drichel, Eva Louwersheimer, Markus P. Kummer, Carlos Cruchaga, Per Hoffmann, Charlotte E. Teunissen, Henne Holstege, Johannes Kornhuber, Oliver Peters, Adam C. Naj, Vincent Chouraki, Céline Bellenguez, Amy Gerrish, Reiner Heun, Lutz Frölich, Michael Hüll, Lara Buscemi, Stefan Herms, Heike Kölsch, Philip Scheltens, Monique M.B. Breteler, Eckart Rüther, Jens Wiltfang, Alison Goate, Frank Jessen, Wolfgang Maier, Michael T. Heneka, Tim Becker, Markus M. Nöthen

Bibliographic record

VenueHuman Molecular Genetics · 2014
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsnot available
FundersNational Institute on AgingCanadian Institutes of Health ResearchBundesministerium für Bildung und ForschungDeutsche Forschungsgemeinschaft
KeywordsApolipoprotein EDementiaBiologyMicrogliaSingle-nucleotide polymorphismCerebrospinal fluidCognitive declineInternal medicineGenotypeDiseaseAlzheimer's diseaseNeurocognitiveOncologyEndocrinologyCognitionImmunologyMedicineGeneticsNeuroscienceGene

Abstract

fetched live from OpenAlex

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.038
GPT teacher head0.366
Teacher spread0.328 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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

Citations52
Published2014
Admission routes1
Has abstractyes

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