A mouse model of early sporadic tau pathology induces neurogenic plasticity in the hippocampus
Bibliographic record
Abstract
Alzheimer's disease varies by sex but is broadly characterized by widespread neurodegeneration and the accumulation of insoluble amyloid plaques and neurofibrillary tangles. However, at the earliest stages of the disease cell death and pathological tau are localized to the entorhinal cortex. In particular, the lateral entorhinal cortex, and its functions in object-related memory, are among the most vulnerable in aging. Notably, the entorhinal cortex projects directly to the dentate gyrus subregion of the hippocampus, where neurogenesis proceeds throughout adult life. Immature, adult-born neurons provide plasticity at the entorhinal-dentate pathway and they may be uniquely responsive, or vulnerable, to early entorhinal tau pathology. To test this, we injected a human tau-expressing recombinant adeno-associated virus (hTau) into the lateral entorhinal cortex and used male and female AsclCreER mice to birthdate downstream dentate neurons born in early postnatal development or adulthood. Consistent with known roles in neurodegeneration, lateral entorhinal hTau expression caused a loss of mushroom spines in downstream dentate gyrus neurons of male and female mice and reduced dendritic complexity of adult-born neurons in male mice. Presynaptic hTau also increased neurogenesis levels and increased the density of thin spines on adult-born neurons in both male and female mice. Consistent with spine addition, hTau increased the slope of the synaptic input-output curves; amongst adult-born neurons, this was due to a specific effect on synapses in male mice. hTau did not alter the magnitude of long-term potentiation at entorhinal synapses onto adult- or developmentally-born neurons. Thus, in a novel model of early sporadic tau pathology, there are changes consistent with neurodegeneration but also compensatory neuroplastic changes, caused in part by neurogenesis. Since immature neurons have also been identified in the human dentate gyrus, a similar neurogenic plasticity may help maintain entorhinal-hippocampal formation in pathological aging.
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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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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".