P2‐118: Liver X receptors ligand and minocycline: Effectiveness of combined drug therapy in an Alzheimer's transgenic mouse model
Bibliographic record
Abstract
Alzheimer's disease (AD) is a multifactorial disorder (combination of genes and environmental factors) and apparently involves several different etiopathogenic mechanisms. Currently, there is no effective treatment to halt the progression or prevent the onset of AD. A number of theories involving various risk factors such as diet, lifestyle, socioeconomic status, genetic predisposition and head injury have been proposed, but the degree of contribution of each factor is still controversial. Along with age, several factors appear to be widely acknowledged as early risk factors for development of AD including chronic neuroinflammation, brain oxidative damage, hypercholesterolemia and Apolipoprotein E. On the other hand, there is a solid body of scientific evidence that the progressive brain accumulation of the peptide Abeta is key to the AD neuropathology. In recent studies, the initiation and progression of AD has been linked to neuroinflammation, cholesterol metabolism (including APOE activity) and Abeta accumulation, processes that can be modulated by minocycline and liver x receptors (LXRs). This study is aimed to test the effectiveness of the combined daily administration of minocycline with LXRs agonist (during four weeks) to establish the extent of the benefits of the combined therapy (synergism), as opposed to monotherapy with the two above-mentioned agents in our AD-like transgenic mouse model coded McGill-Thy1-APP. We have been able to demonstrate and replicate the known beneficial CNS effects of minocycline treatment as an antioxidant and anti-inflammatory agent in our transgenic AD mouse model. Moreover, we have confirmed that Liver X receptor (LXRs) agonists' treatment in our AD transgenic mouse model reverse cognitive deficits and facilitated the proteolytic degradation of Abeta, without inducing hepatic steatosis and hypertriglyceridemia. When combined, animals receiving both agents simultaneously, displayed a marked reduction of cortical peroxynitrite-mediated oxidative damage, lowered burden of Aβ and decreased pro-inflammatory markers (IL-1β). This preliminary study provides evidence of the benefits of the combined therapy (synergism), as opposed to monotherapy with minocycline and LXRs agonist in our AD-like transgenic mouse model. These observations suggest that the combined administration may represent a promising therapeutic opportunity.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 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".