Astrocyte reactivity and cerebral glucose hypermetabolism in early Alzheimer's: insights from a longitudinal study in the TgF344‐AD rat model
Bibliographic record
Abstract
Abstract Background Recent studies have suggested a transient glucose hypermetabolism in early phases of Alzheimer's Disease (AD), which is followed by a characteristic glucose hypometabolism in dementia stages. This phenomenon desveres further investigation and it is suggested to be associated to glial/inflammatory or compensatory neuronal responses. Here, we aimed to longitudinally investigate brain glucose metabolism in an AD animal model and explore associated cellular and inflammatory changes. Method Longitudinal assessments, including cerebral glucose metabolism (18F]FDG‐PET), behavioral tasks and cerebrospinal fluid (CSF) sample collection were performed at 3, 6, 9, and 12 months of age (mo) in wild type (WT) and TgF344‐AD rats (Tg). Glial and inflammatory markers were evaluated in the CSF via ELISA multiplex. A cross‐sectional cohort was used to follow the spatial distribution of Aß plaques (IHC), to assess the brain content of glial and neuronal proteins (western blot), and to analyze the cortical glutamate uptake (ex‐vivo slices) at the same time points. Result At 9mo, three months after the initial appearance of Aß plaque deposits, Tg animals exhibited cortical glucose hypermetabolism (Figure 1A‐C). At the same age, astrocytic glutamate uptake was increased in the cortex and hippocampus (Figure 2). Declines in performance on the Y‐maze and Novel Object Recognition tasks were observed at 9 and 12mo (Figure 1D). CSF analysis revealed elevated GFAP levels at 6, 9 and 12mo, and reduced S100B at 9mo (Figure 1E e F). Tissue GFAP immunocontent increased in the temporoparietal cortex at 6 and 9mo, in the hippocampus at 9mo, and was reduced in the frontal and temporoparietal cortices at 12mo (Figure 3). Conclusion Our findings suggest the presence of an early, transient phase of brain glucose hypermetabolism in TgF344‐AD rats, consistent with observations in recent animal and human studies. This phenomenon seems to be closely linked to the astrocyte response, reflected in variations of crucial astrocyte proteins such as GFAP and S100B, along with an increase in the glutamate uptake by these cells. In contrast, neuronal, microglial and inflammatory markers did not exhibit changes during this timeframe.
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 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) | 0.000 | 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".