Non‐steroidal anti‐inflammatory drugs mediate increased <i>in vitro</i> glial expression of apolipoprotein E protein
Bibliographic record
Abstract
Epidemiological studies have shown that use of non-steroidal anti-inflammatory drugs (NSAIDs) by the elderly is associated with a decreased relative risk and a delayed onset of Alzheimer's disease (AD). In contrast, the apolipoprotein E (apoE) gene has proven to be a risk factor for AD with apoE epsilon 4 AD patients having been found to show lower levels of brain apoE. In the present study, treatment of primary rat mixed glial cell cultures with the common NSAIDs, indomethacin and aspirin, induced significant increases in extracellular apoE protein levels. Similarly, treatment of primary rat astrocyte cell cultures with aspirin and a cyclooxygenase (COX)-2-selective aspirin derivative also stimulated significant increases in apoE protein. However, astrocyte and mixed glial apoE protein levels were significantly reduced following exposure to COX-2-specific indomethacin amides and an inactive indomethacin derivative. ApoE protein modulation was observed at physiological and subphysiological concentrations well below the COX inhibition IC50 values of the NSAIDs used, suggestive of a COX-independent mechanism. In contrast to these results, indomethacin and aspirin treatment failed to induce any significant changes in apoE mRNA levels. The failure of NSAIDs to significantly alter apoE expression may have been indicative of a nontranscriptional mechanism of apoE protein induction. Consequently, NSAID-induced increases in apoE protein may enhance apoE-mediated immunosuppression and compensatory synaptic plasticity, potentially resulting in decreased AD risk and delay of disease onset.
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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) | 0.000 | 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) | 0.002 | 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".