Characterizing metabolic, behavioural, and bone changes in a novel aging mouse model of sporadic Alzheimer’s disease
Bibliographic record
Abstract
BACKGROUND: Alzheimer's disease (AD) is linked to comorbidities such as osteoporosis, sarcopenia, and type II diabetes. Currently, there is a lack of mouse models that mimic sporadic AD (sAD) which accounts for ∼95% of AD cases. A new humanized mouse model (hAb) was developed by substituting 3 amino acids in the amyloid beta sequence to the human counterpart. These mice develop an age-dependent sAD like pathology. This study characterized age-related changes in body composition, energy expenditure (EE), movement, bone health, glucose tolerance and insulin sensitivity prior to the development of sAD in the hAb mice. METHODS: Wild type (WT) and hAb mice (n =10 per group) were characterized from 4 to 16 months of age. At the age of 4 months, and repeated every two months, body mass, whole body lean and fat mass, and the bone mineral density (BMD) of whole body, tibia, femur, and lumbar vertebrae 1-5 were measured using dual-energy X ray absorptiometry (DXA). Glucose and insulin tolerance testing (GTT & ITT) were also performed. EE and movement were measured using metabolic caging, and novel object recognition (NORT) and location (NOLT) testing were performed at age 4 and 16 months. RESULTS: The hAb mice significantly gained more weight and fat compared to WT throughout aging. They also had significantly lower percentage of lean mass and faster rates of lean mass decline throughout aging compared to the WT mice. EE and movement were also lower in the hAb mice. No genotype effects were seen in whole body and regional BMD or the area under the curve for GTT and ITT. The hAb mice spent less time with the novel object in the NORT and NOLT, however this result was not significant. CONCLUSION: The increased fat, and decreased percentage of lean mass along with reduced movement and energy expenditure in the hAb mice may indicate metabolic dysfunction which may precede sAD development. Future steps include increasing the sample size and investigating sex differences between the hAb female and male mice to determine any sex specific changes.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".