Tau Pathology in the Entorhinal‐Hippocampal Circuit
Bibliographic record
Abstract
Abstract Background The lateral entorhinal cortex (LEC) is the site of tau accumulation in early stages of Alzheimer’s disease and has projections downstream to the dentate gyrus (DG) of the hippocampus. The pathological form of tau has the ability to propagate across synapses, spreading to connected brain regions and correlating with memory deficits and synaptic loss. Downstream to the LEC, the hippocampal DG is the site of ongoing adult neurogenesis, with new granule neurons added showing enhanced plasticity and increased survival compared to older neurons. We are interested in examining the role of neuron age for vulnerability to tau pathology in the LEC‐DG circuit. Method We use a transgenic mouse model to label neurons born at different ages in the DG (development vs. adulthood) with a fluorescent reporter and inject a human Tau‐expressing virus, or control virus, into the LEC directly to mimic early, localized tau pathology. Following a 4‐month incubation, animals are tested for memory deficits specific to the LEC and hippocampus with Novel Object Recognition (NOR) and Novel Place Recognition (NPR) and tissue is immunohistochemically processed to analyze tau levels and cellular morphology in fluorescent‐labelled DG neurons. We assess synaptic changes in DG neurons via measuring dendritic spines, dendritic complexity and mossy fibre boutons. Result Our findings demonstrate that tau animals perform worse on NOR compared to healthy controls, while no difference is found for NPR. Morphological results show adult‐born neurons have an increase in thin dendritic spines and decrease in mushroom spines in tau animals relative to controls, as well as reduced mossy fibre bouton filopodia length. Conclusion Our initial results demonstrate the effect of tau on the LEC‐DG circuit, with altered synaptic structures and impaired memory performance under tau pathology.
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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 | 0.000 |
| 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".