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Record W4387618437 · doi:10.1136/jnnp-2023-331854

Alzheimer’s disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI

2023· article· en· W4387618437 on OpenAlexfundno aff
Neil Graham, Karl Zimmerman, Amanda Heslegrave, Ashvini Keshavan, Federico Moro, Samia Abed‐Maillard, Adriano Bernini, Vincent Dunet, Elena Garbero, Giovanni Nattino, Arturo Chieregato, Enrico Fainardi, Camelia Baciu, Primož Gradišek, Sandra Magnoni, Mauro Oddo, Guido Bertolini, Jonathan M. Schott, Henrik Zetterberg, David Sharp

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2023
Typearticle
Languageen
FieldMedicine
TopicTraumatic Brain Injury Research
Canadian institutionsnot available
FundersMedical Research CouncilHORIZON EUROPE Framework ProgrammeOlav Thon StiftelsenUK Dementia Research InstituteFamiljen Erling-Perssons StiftelseEuropean CommissionHjärnfondenVetenskapsrådetEisaiApellis PharmaceuticalsSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungWolfson FoundationImperial College Healthcare NHS TrustUniversity College LondonBritish Heart FoundationNovo NordiskNational Institute for Health and Care ResearchAcademy of Medical SciencesWeston Brain InstituteAlzheimer's Drug Discovery FoundationBrain Research UKEU Joint Programme – Neurodegenerative Disease ResearchAlzheimer's AssociationStiftelsen för Gamla TjänarinnorBiogenImperial College LondonNational Science FoundationProthena
KeywordsTraumatic brain injuryAtrophyChronic traumatic encephalopathyMedicineNeurodegenerationInternal medicineGlial fibrillary acidic proteinPathologyWhite matterTau proteinNeurofilamentGastroenterologyAlzheimer's diseaseMagnetic resonance imagingDiseasePoison controlPsychiatryImmunohistochemistryConcussion

Abstract

fetched live from OpenAlex

BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.

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)0.000
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 score0.003
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.048
GPT teacher head0.314
Teacher spread0.266 · 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

Citations7
Published2023
Admission routes1
Has abstractyes

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