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Record W4386212103 · doi:10.1038/s41467-023-40937-z

Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases

2023· article· en· W4386212103 on OpenAlexaff
Erik Nutma, Nurun Fancy, Maria Weinert, Stergios Tsartsalis, Manuel Marzin, Robert C. J. Muirhead, Irene Falk, Marjolein Breur, Joy de Bruin, David Hollaus, Robin Pieterman, Jasper J. Anink, David Story, Siddharthan Chandran, Jiabin Tang, Maria Chiara Trolese, Takashi Saito, Takaomi C. Saido, Katharine Wiltshire, Paula Beltran-Lobo, Alexandra Phillips, Jack P. Antel, Luke M. Healy, Marie‐France Dorion, Dylan A. Galloway, Rochelle Y. Benoit, Quentin Amossé, Kelly Ceyzériat, Aurélien M. Badina, Enikò Kövari, Caterina Bendotti, Eleonora Aronica, Carola I. Radulescu, Jia Hui Wong, Anna M. Barron, Amy M. Smith, Samuel J. Barnes, David W. Hampton, Paul van der Valk, Steven Jacobson, Owain W. Howell, David Baker, Markus Kipp, Hannes Kaddatz, Benjamin B. Tournier, P. Millet, Paul M. Matthews, Craig S. Moore, Sandra Amor, David R. Owen

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldNeuroscience
TopicNeuroinflammation and Neurodegeneration Mechanisms
Canadian institutionsMemorial University of NewfoundlandMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Institute on AgingMedical Research CouncilNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Science FoundationImperial College Healthcare NHS TrustImperial College LondonMultiple Sclerosis SocietyUK Dementia Research InstituteNational Institute for Health and Care ResearchUniversity of OxfordIsrael Cancer Research FundAlzheimer's SocietyRush University
KeywordsTranslocator proteinMicrogliaBiologyTranscription factorInflammationAP-1 transcription factorNeuroinflammationNeuroscienceHuman brainCell biologyImmunologyGeneGenetics

Abstract

fetched live from OpenAlex

Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.036
Threshold uncertainty score0.889

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

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 head0.062
GPT teacher head0.318
Teacher spread0.256 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations182
Published2023
Admission routes1
Has abstractyes

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