Co‐localization of tau and <scp>TDP</scp> ‐43 after extracellular vesicle delivery to cells
Bibliographic record
Abstract
Perturbations in the metabolism of microtubule‐associated protein tau (tau) underlie the pathology of a broad array of dementias, including chronic traumatic encephalopathy, amyotrophic lateral sclerosis (ALS) with cognitive impairment (ALSci) and approximately half of the dementias associated with frontotemporal lobar degeneration. We recently observed significantly increased hippocampal tau pathology in rats injected with pseudophosphorylated human tau (2N4R tau T175D ) co‐expressing an ALS‐associated TAR DNA‐binding protein 43 (TDP‐43) mutant (TDP‐43 M337V ) when compared to wild‐type rats. To understand this mechanism, we examined whether the extracellular vesicles (EVs) derived from wild‐type TDP‐43 (wtTDP‐43) or tau‐expressing cells could transfer expression of these proteins to recipient cells, and whether co‐localization of these proteins occurs. mCherry‐ wt TDP‐43 or EGFP‐tau constructs were expressed in HEK293 or SH‐SY5Y cells. The secretome and EV fractions contained wt TDP‐43 or 2N4R tau protein and RNA, and could transfer proteins into nontransfected cells. Co‐localization was also detected in the cytosol of recipient cells. In silico modeling of tau and TDP‐43 interactions suggests hydrogen bonding underlies this interaction. These studies further our understanding of the interaction between tau and TDP‐43 by demonstrating their ability to co‐aggregate and in providing a mechanism by which cell–cell transfer of either protein via extracellular vesicles can lead to these synergistic interactions.
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 imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.000 | 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 teacher head, 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".