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Record W4409449256 · doi:10.1093/brain/awaf135

Midbrain cytotoxic T cells as a distinct neuropathological feature of progressive supranuclear palsy

2025· article· en· W4409449256 on OpenAlexafffund
Blas Couto, Shelley L. Forrest, Conor Fearon, Seojin Lee, Samantha Knott, Jun Li, Susan H. Fox, Maria Carmela Tartaglia, Anthony E. Lang, Gábor G. Kovács

Bibliographic record

VenueBrain · 2025
Typearticle
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsOntario Brain InstituteUniversity Health NetworkToronto Western HospitalOccupational Cancer Research CentreUniversity of Toronto
FundersParkinsonfondenNational Institutes of HealthRossy FoundationNovo NordiskEisaiMultiple System Atrophy CoalitionUniversity of CambridgeJohns Hopkins UniversitySun PharmaFondation Brain CanadaFamily Larsson‐Rosenquist FoundationBiogenCanadian Institutes of Health ResearchParkinson CanadaEdmond J. Safra Philanthropic FoundationKrembil FoundationCanada Foundation for InnovationOntario Research FoundationEli Lilly and Company
KeywordsProgressive supranuclear palsyCytotoxic T cellSubstantia nigraPathologyTegmentumMicrogliaParkinson's diseaseCD8NeuropathologyBiologyMidbrainNeuroscienceMedicineImmunologyCentral nervous systemInflammationImmune systemDisease

Abstract

fetched live from OpenAlex

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by four-repeat (4R) tau protein deposition. The substantia nigra (SN) and midbrain tegmentum nuclei (MBT) are consistently affected. Lymphocyte infiltrates are scarce in the brains of patients with neurodegenerative diseases, although a few reports have described their presence in the α-synucleinopathy Parkinson's disease (PD). To evaluate the cytotoxic T-cell response, serial sections spanning 120 μm of the SN were immunostained consecutively for phosphorylated tau (p-tau, AT8) or α-synuclein, cytotoxic T-cell marker and microglia marker HLA-DR. Sections were analysed with stereology software in 9 patients with PSP, 10 with PD and 6 healthy controls. We semiquantitatively scored CD8-positive cells in further brain regions. CD8 lymphocyte cell counts and microglial activation in the SN were higher in PSP than PD and controls. Furthermore, T-cell/neuron contact was observed in PSP. In multivariate models, CD8 counts were not predicted by disease duration, younger age at death or the amount of p-tau pathology. The SN and midbrain tegmentum showed more CD8 cells than the cortex. A more prominent nigral cytotoxic T-cell response in PSP than PD supports the suggestion that p-tau neuropathology in PSP might have potential relationships with autoimmune mechanisms.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.690
Threshold uncertainty score0.584

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.010
GPT teacher head0.281
Teacher spread0.271 · 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

Citations9
Published2025
Admission routes2
Has abstractyes

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