Bibliographic record
Abstract
Abstract Background Monitoring tau propagation in the living brain has important pathophysiological and therapeutic implications. Previous studies assessing tau propagation relied on cross‐sectional immunohistochemical techniques in post‐mortem tissue, as such little is known regarding the behaviour of tau preparations in living systems. As tau imaging agents are dependent on tau conformations, we aim to determine the tau species amenable to in vivo imaging. As such, the goal of this work is to examine the binding properties of [18F]MK‐6240, a second‐generation tau imaging agent in different tau preparations. Method Seven Fisher 344 rats (15± 0.25 months) were used. All animal had a baseline scan with [18F]MK6240 before the stereotaxic tau injections. We tested various recombinant human tau PFFs and patient derived AD‐tau following gel extraction or serial filtration extraction. All tau preparations were stereotaxically injected in the dorsal hippocampus (DV: ‐3.5; AP: ‐3.5; ML:‐2). All recombinant tau PFFs had an injection volume of 2uL and concentration of 4ug/uL, whereas AD‐tau had an injection volume of 2uL and a concentration of 0.4 ug/uL. Structural MRI were conducted following surgery to determine the final position of the injection site. All animals underwent to a 1 hour dynamic acquisition PET with [18F]MK6240. The non‐displaceable binding potential (BPND) images were generated using cerebellar grey as a reference region based on Simplified Reference Tissue Method (SRTM). The comparison of the images was conducted using z‐scores. Result We injected a total of 7 rats with varying tau extracts. We found that the hemispheres injected with human tau extracts from both filtration and gel electrophoresis preparation method showed positive BPnd signals versus hemispheres with control injections. Both recombinant human tau PFF’s lacking FTD‐mutations show positive [18F]MK‐6240. The entire procedure was well tolerated by the animals. Conclusion These results reveal that PET [18F]MK‐6240 constitutes a promising method for quantification of tau seeding and propagation in the rat brain. Not all tau preparations provide binding sites for [18F]MK6240 binding. Future longitudinal studies will reveal whether these techniques will be able to capture tau propagation.
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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) | 0.001 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".