IC‐P‐045: Cerebral glucose metabolism, pathology and behavior in the 5XFAD mouse model of Alzheimer's disease
Bibliographic record
Abstract
A pathological hallmark of Alzheimer's disease (AD) is the deposition of β-amyloid (Aβ) plaques in the brain. The five times familial AD (5XFAD) mouse model is an aggressive model of brain amyloidosis. We hypothesized that the 5XFAD mouse would display changes in brain glucose metabolism compared to age-matched controls, and that these changes would be correlated with brain pathology and behavioural dysfunction. Recapitulating aspects of human AD in a mouse model at an early age will facilitate evaluation of diagnostics and therapeutics for this disease. Male 5XFAD mice and age-matched wild-type controls were injected with 18 F-FDG and imaged using PET, CT and MRI scans. The PET/CT/MRI fused data was co-registered to an MRI atlas for parcellation of specific brain regions. After decay of the isotope, the animals were perfused, the brains removed and cut in 40 um serial sections which were stained, using immunohistochemical methods, for Aβ and microglia (Iba-1). Visuo-spatial learning and memory and motor ability were assessed with the Morris water maze and rota-rod, respectively. FDG-PET imaging of the 5XFAD mice revealed a pattern of age-dependent altered brain metabolism compared to age-matched controls. β-amyloid staining revealed significant and widespread accumulation of Aβ plaques throughout the brain in the 5XFAD mice. Microglial response was elevated in aged animals and may be a contributing factor to the FDG uptake patterns observed in the brain. Modest impairments in learning and memory were observed at 6 months of age in the 5XFAD mice, while severe motor impairments were present after 12 months of age. The 5XFAD mouse develops an AD phenotype early in life. Similar to human AD, altered brain metabolism was observed in these mice compared to age matched controls. The 5XFAD mice displayed robust plaque pathology and microglial response that recapitulated characteristics of human AD. The most profound change in behavioural phenotype was motor impairment after 12 months of age. The 5XFAD mouse model may be a powerful tool for assessing efficacy of diagnostic and therapeutic agents being developed for AD.
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 | 0.001 | 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 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".