Unique features of microglial response in Progressive Supranuclear Palsy
Bibliographic record
Abstract
BACKGROUND: Microglia play a crucial role in neurodegenerative diseases, but their specific involvement in disease progression remains unclear. Microglial diversity, initially described by Río-Hortega as varied morphological features, has been further explored through single-cell analyses identifying multiple subtypes. These findings suggest microglia exhibit diverse morphological and functional changes depending on pathological conditions even within the same disease. However, there is a paucity of data on progressive supranuclear palsy a (PSP), a tauopathy characterized by neuronal and glial tau pathologies. METHOD: This study investigates the role of microglia in the frontal cortex of PSP. We performed immunohistochemistry for Iba1 and HLA-DR microglial markers in nine PSP cases and nine age-matched controls. Quantitative evaluation of positive regions in the cortex and white matter was conducted using HALO®. Morphological analysis of Iba1-positive cells was performed with the HALO Microglial Activation Module. The snRNA-seq on frozen samples from three PSP and three controls identified differentially expressed genes (DEGs) and GO enrichment. PSP-specific microglial subclusters were compared with previously reported subtypes (DAM, MgND, HAM). RESULT: Iba1-positive microglia load is significantly increased only in the white matter in PSP, while HLA-DR-positive microglia load is increased in both the cortex and white matter. Microglia in PSP exhibited significantly longer processes, more branching, and larger cell bodies, particularly in the white matter. The snRNA-seq identified four PSP-specific subclusters, including those with high homeostatic gene expression (SC0), MHC class II pathway activation (SC0, 2, 4) and clusters enriched with aging-related genes (SC5). GO enrichment revealed functional diversity, including clusters enriched with aging-related genes. Modulation scoring did not reveal clear similarities with previously reported microglial subtype gene sets. CONCLUSION: This study reveals unique microglial morphological and functional characteristics in the PSP affected frontal cortex.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".