Temporal evaluation of imaging and biofluid biomarkers, spatial neuropathology and glial function in the TgF344‐AD rat model
Bibliographic record
Abstract
Abstract Background The development and characterization of Alzheimer’s disease (AD) animal models is particularly important for the investigation of pathophysiological mechanisms and drug development. The TgF344‐AD rat is a model harboring human APP/PS1 mutations with comprehensive presentation, including age‐dependent development of amyloid‐β (Aβ) plaques, neuronal loss and tau deposits, but not yet fully characterized. In light of this, we evaluated imaging and biofluid biomarkers, spatial neuropathology and glial function in these animals across multiple key ages. Methods TgF344‐AD rats and wild‐type littermates were longitudinally evaluated at 3, 6, 9, 12 and 16‐18 months of age. Rats underwent [18F]FDG‐microPET scans and CSF samplings. CSF glial and immune markers (GFAP, S100B, TREM2, IL‐6, TNF‐α, IL‐10) were measured by multiplex immunoassay. A cross‐sectional cohort was used to measure cortical glutamate uptake (ex‐vivo slices) and follow the spatial distribution of Aβ plaques (6E10 antibody) at the same time points. Results At 3, 6, 12 and 16‐18mo, no changes in [18F]FDG metabolism were observed. At 9mo, we identified a significant cortical hypermetabolism in the TgF344‐AD rats. CSF GFAP levels were elevated at 6 and 9 months of age, while CSF S100B was decreased at 9mo. The CSF inflammatory markers IL‐6, TNF‐α and IL‐10 were elevated at 16‐18mo. Additionally, the glutamate uptake was increased in the cortex at 9mo and 12mo, and in the hippocampus at 12mo. TREM2 was not altered in any of the ages evaluated. The (Aβ) plaques deposition starts at 6mo in the posterior temporal cortices and hippocampus and spreads slowly to frontal brain regions, reaching a plateau around 16mo. Conclusion This work shows that the TgF344‐AD rat model recapitulates the early and transient glucose hypermetabolism seen in AD patients. Our results also indicate an associated early astrocyte response in these animals, with changes in relevant astrocyte biomarkers and function (glutamate uptake). Due to the critical role of astrocytes in brain glucose handling, these findings suggest that astrocyte reactivity could be driving glucose hypermetabolism. In contrast, the neuroinflammatory biomarkers changes identified suggest a strong neuroinflammatory response only at later stages in this rat model, however, further investigations are necessary to better elucidate these findings.
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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 | 0.001 |
| 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".