Ube3a deficiency inhibits amyloid plaque formation in APPswe/PS1δE9 mouse model of Alzheimer’s disease
Bibliographic record
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in memory and cognitive function. Pathological hallmark of AD includes aberrant aggregation of amyloid beta (A) peptide, which is produced upon sequential cleavage of amyloid precursor protein (APP) by -and -secretases. On the contrary, -secretase cleaves APP within the A sequence and thereby prevents A generation. Here, we investigated the role of ubiquitin ligase Ube3a (involved in synaptic function and plasticity) in the pathogenesis of AD using APPswe/PS1E9 transgenic mouse model and first noticed that soluble pool of Ube3a was age dependently decreased in AD mouse in comparison with wild type controls. To further explore the role of Ube3a in AD patho-mechanism, we generated brain Ube3a-deficient AD mice that exhibited accelerated cognitive and motor deficits compared to AD mice. Interestingly, these Ube3a-deficient AD mice were excessively obese from their age of 12 months and having shorter lifespan. Biochemical analysis revealed that the Ube3a-deficient AD mice had significantly reduced level of A generation and amyloid plaque formation in their brain compared to age-matched AD mice and this effect could be due to the increased activity of -secretase, ADAM10 (a disintegrin and metalloproteinase-10) that shift the proteolysis of APP towards non-amyloidogenic pathway. These findings suggest that aberrant function of Ube3a could influence the progression of AD and restoring normal level of Ube3a might be beneficial for AD.
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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 | 0.000 | 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 | 0.001 | 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".