Ciclosonide reduces lipid droplet burden in APOE4 astrocytes
Bibliographic record
Abstract
BACKGROUND: Prior studies have shown that ApoE ε4 astrocytes display a higher LD count than ApoE ε3 astrocytes. We examined the effects of pharmacological agents on lipid droplets (LDs) in apolipoprotein E (ApoE) ε3 and ApoE ε4 astrocytes. METHOD: We hypothesized that drugs reducing LDs in ApoE ε4 astrocytes could reveal mechanisms of LD formation and inform potential treatments for AD. A screen of 2,321 FDA-approved drugs was conducted to identify candidates for investigating LD differences between ApoE ε3 and ApoE ε4 astrocytes. RESULT: Both ApoE ε3 and ApoE ε4 astrocytes produced LDs detectable with BODIPY staining. PLIN2 co-staining ensured LD specificity. A drug screen and validation workflow identified three compounds, ciclosonide, VX745, and ipragliflozine, as reducing LDs in ApoE ε4 astrocytes specifically. Ciclesonide, a glucocorticoid with a known mechanism of action, showed dose-dependent effects on LD reduction (0.05, 0.5, and 5 mM). Transcriptomic analysis of ciclesonide-treated astrocytes revealed significant changes in extracellular matrix organization. CONCLUSION: These findings enhance understanding of LD formation and isoform-specific differences in astrocytes. Given the role of LDs in AD, these insights may contribute to understanding AD pathogenesis and identifying therapeutic strategies.
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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) | 0.000 | 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) | 0.001 | 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".