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Record W4413807727 · doi:10.1038/s41467-025-63545-5

CSF total tau as a proxy of synaptic degeneration

2025· article· en· W4413807727 on OpenAlexafffund
Carolina Soares, Bruna Bellaver, Pâmela C.L. Ferreira, Guilherme Povala, Cristiano Schaffer Aguzzoli, João Pedro Ferrari‐Souza, Hussein Zalzale, Firoza Z Lussier, Francieli Rohden, Sarah Abbas, Guilherme Bauer‐Negrini, Douglas Teixeira Leffa, Andréa Lessa Benedet, Rebecca Langhough, Tobey J. Betthauser, Bradley T. Christian, Rachael E. Wilson, Dana Tudorascu, Pedro Rosa‐Neto, Thomas K. Karikari, Henrik Zetterberg, Kaj Blennow, Eduardo R. Zimmer, Sterling C. Johnson, Tharick A. Pascoal

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsMcGill UniversityCentre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalMontreal Neurological Institute and Hospital
FundersNational Institute of Mental HealthNational Institute on AgingFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchInstituto SerrapilheiraFamiljen Erling-Perssons StiftelseHjärnfondenEuropean CommissionHORIZON EUROPE Framework ProgrammeAlzheimer's SocietyMinistério da Ciência, Tecnologia e InovaçãoCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorGlobal Brain Health InstituteEU Joint Programme – Neurodegenerative Disease ResearchUK Dementia Research InstituteFundação de Amparo à Pesquisa do Estado do Rio Grande do SulNational Academy of NeuropsychologyAlzheimer's AssociationStiftelsen för Gamla TjänarinnorConselho Nacional de Desenvolvimento Científico e TecnológicoNational Institute of Neurological Disorders and StrokeUniversity of PittsburghConsortium canadien en neurodégénérescence associée au vieillissementAlzheimerfondenWeston Brain InstituteAlzheimer's Drug Discovery FoundationNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsProxy (statistics)Degeneration (medical)NeuroscienceBiologyComputer scienceMedicinePathology

Abstract

fetched live from OpenAlex

Cerebrospinal fluid (CSF) total tau (t-tau) is considered a biomarker of neuronal degeneration alongside brain atrophy and fluid neurofilament light chain protein (NfL) in biomarker models of Alzheimer's disease (AD). However, previous studies show that CSF t-tau correlates strongly with synaptic dysfunction/degeneration biomarkers like neurogranin (Ng) and synaptosomal-associated protein 25 (SNAP25). Here, we compare the association between CSF t-tau and synaptic degeneration and axonal/neuronal degeneration biomarkers in cognitively unimpaired and impaired groups from two independent cohorts. We observe a stronger correlation between CSF t-tau and synaptic biomarkers than neurodegeneration biomarkers in both groups. Synaptic biomarkers explain a greater proportion of variance in CSF t-tau levels compared to neurodegeneration biomarkers. Notably, CSF t-tau levels are elevated in individuals with abnormalities only in synaptic biomarkers, but not in individuals with abnormalities only in neurodegeneration biomarkers. Our findings suggest that CSF t-tau is a closer proxy for synaptic degeneration than for axonal/neuronal degeneration.

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)0.002
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
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
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 head0.022
GPT teacher head0.370
Teacher spread0.348 · 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

Citations6
Published2025
Admission routes2
Has abstractyes

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