Tau spreads across connected brain regions in progressive supranuclear palsy and corticobasal syndrome
Bibliographic record
Abstract
Abstract Background Cortico‐basal degeneration (CBD) and progressive supranuclear palsy (PSP) are 4R‐tauopathies characterized by progressive tau pathology spread that typically starts in the subcortex. Pre‐clinical studies suggest that tau spreads across connected neurons in an activity‐dependent manner, indicating that the brains’ connectome may mediate tau spreading. Supporting this, we found in Alzheimer’s disease that PET‐assessed cortical tau spreads across functionally connected regions. Here, we assessed whether connectivity mediates cortical/subcortical tau spreading also in 4R‐tauopathies, by combining resting‐state fMRI connectivity with i) 2nd generation in vivo tau‐PET (PI2620) in CBS and PSP and ii) post‐mortem tau assessments in PSP. Method We assessed PI2620 tau‐PET in 24 CBS‐patients, 28 PSP‐patients and 15 healthy controls. Voxel‐wise tau‐PET differences were determined between patients vs. controls and mean tau‐PET SUVRs were assessed for 232 cortical/subcortical‐ROIs (Fig. 1A). Semi‐quantitative post‐mortem AT8‐stained neuronal tau was assessed in two additional, non‐overlapping PSP samples (Munich: n=96; & UPENN: n=97). Neuropathological ROIs were reconstructed in MRI‐standard‐space (Figs. 1B&C). Functional connectivity was assessed between tau‐PET‐ROIs and neuropathological‐ROIs using out‐of‐sample resting‐state fMRI from 69 elderly amyloid‐ and tau‐negative controls. Using linear regression, we assessed the association between ROI‐to‐ROI connectivity and covariance in tau‐PET or post‐mortem tau levels in spatially corresponding ROI pairs. For tau‐PET, we further tested at the subject level, whether functional connectivity of tau epicenters (i.e. ROIs with highest tau‐PET in a given subject) predicted tau deposition in connected regions, using linear mixed models controlling for age, gender and random intercept. Result PSP and CBS patients showed elevated tau‐PET compared to controls (Fig. 2). Higher functional connectivity was associated with higher covariance in tau‐PET in PSP and CBS (b=0.402‐0.715, Fig. 3A‐D, all p<0.001). For post‐mortem data, higher ROI‐to‐ROI functional connectivity was also associated higher covariance in tau in both PSP samples (b=0.468&0.765, p<0.001, Fig. 3E&F). Using tau‐PET we found further that connectivity patterns of subject‐level subcortical tau epicenters was associated with subject‐level tau‐PET uptake in connected regions (Fig. 4B‐E, all p<0.001). Conclusion Highly functionally connected brain regions share similar tau levels in 4R‐tauopathies as indicated by tau‐PET and post‐mortem assessments, suggesting that brain connectivity is associated with inter‐regional tau spreading in 4R‐tauopathies.
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 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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".