A Primary Cell Culture‐Based Approach for Studying the Pathophysiology of Progressive Supranuclear Palsy (PSP)
Bibliographic record
Abstract
BACKGROUND: PSP is characterized by 4-repeat tau accumulation in neuronal neurofibrillary tangles, oligodendroglial coiled bodies and in tufted astrocytes (a pathognomonic feature). In PSP, misfolded tau seeds the aggregation of tau throughout the brain in a prion-like manner, with each cytopathology having a distinct, and sometimes overlapping pattern of distribution. The contribution of each of these three distinct cytopathologies to the accumulation and propagation of pathogenic tau throughout the PSP brain is not fully understood. To study this, we will develop a primary culture model of tau cytopathologies in PSP. METHOD: Progenitor cells were isolated from P2-P4 6hTau mice, that express all six human tau isoforms. Cells were cultured in progenitor media and differentiated into astrocytes and neurons using media specific for each cell type and treated with human PSP and Alzheimer's' tau. RESULT: Astrocytes and neurons were labeled with GFAP and MAP2, respectively, to confirm their identity and purity. We will next introduce human brain-derived PSP tau seeds into our cultures to investigate tau uptake and propagation. Initial studies will identify the optimal tau dose for aggregation and potency of tau in these cells. Then, using an astrocyte-neuron co-culture model we will assess how each cell type contributes to tau spread. Finally, we will explore the effects of tau accumulation on neurodegeneration. CONCLUSION: This study presents work towards developing an innovative cell culture model to investigate the role of different cytopathologies in the pathogenesis of PSP. The use of cell cultures enables the future incorporation of live imaging of tau trafficking between astrocytes and neurons. This model aims to deepen our understanding of PSP pathogenesis and provide a valuable platform for testing potential therapeutic strategies.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.004 |
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".