Characterization of Alzheimer's Disease‐like Neuropathology in Duchenne Muscular Dystrophy Using the D2 <i>mdx</i> Mouse Model
Bibliographic record
Abstract
Duchenne Muscular Dystrophy (DMD) is a progressive muscle wasting disorder which affects approximately 1 in 3500 male births and is caused by a mutation in the dystrophin gene. Although most research focuses on the role of dystrophin in skeletal and cardiac muscle, dystrophin is also expressed in the brain, specifically in memory‐associated brain regions like the hippocampus and cortex. Furthermore, patients with DMD and mdx mice (rodent model of DMD) exhibit significant memory and learning impairments, implicating dystrophin loss in neurodegeneration. A recent study found patients with DMD had higher serum amyloid‐β42, with this marker being heavily associated with cognitive impairments and Alzheimer's disease pathology. The purpose of this study was to characterize the neuropathology associated with DMD, focusing on markers of amyloidogenesis and synaptic function, in a preclinical mdx mouse model. Male mdx and age matched (8‐9 weeks old) wild‐type (DBA‐2J) mice were purchased from Jackson laboratories (n = 12 per group). Novel object recognition testing (NORT) was performed to determine cognitive function. Prefrontal cortex and hippocampus brain regions were extracted for analysis. NORT testing demonstrated that mdx mice had reduced exploration time of the novel object (WT 35.2 sec vs mdx 18.7 sec; p = 0.02) and a lower exploration index (‐25%, p < 0.05) compared to WT mice. Western blot analysis revealed higher soluble APP β (+40%) and total APP (+20%) in the prefrontal cortex of mdx mice compared to WT, and lower soluble APP α (‐30%) fragment in the hippocampus (p <0.05). Furthermore, PSD95 content was nearly 2‐fold higher in the prefrontal cortex of mdx mice compared to WT (p <0.05). This study provides novel information about the cellular pathways associated with memory impairment with DMD. Specifically, we show a shift towards amyloidogenesis in the prefrontal cortex and hippocampus brain regions of mdx mice, suggesting the possibility of similar pathogenesis to Alzheimer's disease. These changes are accompanied by reduced performance in the NORT test. Importantly, our results demonstrate that these changes occur at a relatively young age in D2 mdx mice, similar to what is observed in patients with DMD.
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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 | 0.000 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".