Age‐dependent impairment of glucose tolerance in the 3xTg‐AD mouse model of Alzheimer's disease
Bibliographic record
Abstract
ABSTRACT Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple‐transgenic (3xTg)‐AD mouse model of AD, compared with those in nontransgenic (non‐Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical Aβ accumulation (2‐and 3.5‐fold increase in Aβ42 in the soluble and insoluble protein fractions, respectively) in female 3xTg‐AD mice than in the males. Furthermore, female 3xTg‐AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non‐Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5‐fold from 6 to 14 mo of age in female 3xTg‐AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg‐AD mice. The present results suggest that AD‐like neuropathology extends to the pancreas in the 3xTg‐AD mouse, leading to glucose intolerance and contributing to a pathologic self‐amplifying loop between AD and T2D.—Vandal, M., White, P. J., Chevrier, G., Tremblay, C., St‐Amour, I., Planel, E., Marette, A., Calon, F. Age‐dependent impairment of glucose tolerance in the 3xTg‐AD mouse model of Alzheimer's disease. FASEB J. 29, 4273‐4284 (2015). www.fasebj.org
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".