Relationships between CYP450‐sEH oxylipins, small vessel disease markers, and regional neuroimaging in Alzheimer’s disease and mild cognitive impairment
Bibliographic record
Abstract
Abstract Background Cytochrome P450 (CYP450) derived epoxides are vasoactive lipid mediators that may confer neuroprotective and anti‐inflammatory effects. CYP450 epoxides are degraded by soluble epoxide hydrolase (sEH) into diols. This study investigated relationships of these CYP450‐sEH “oxylipins” with regional small vessel disease (SVD) markers, atrophy, and white matter microstructural integrity in people with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) due to AD. Method Participants with clinical AD or MCI were identified from the Ontario Neurodegenerative Disease Research Initiative. Fasting serum oxylipins were quantified using ultra‐high performance liquid chromatography‐tandem mass spectrometry. White matter hyperintensities (WMH), lacunes, perivascular spaces (PVS), and brain parenchymal fraction (BPF) were quantified using structural magnetic resonance imaging. Fractional anisotropy (FA) and mean diffusivity (MD) were measured using diffusion tensor imaging. Spearman correlations were performed between oxylipin species and imaging measures, controlling for demographic factors, ApoE4 status, glucose, cholesterol, systolic blood pressure, and waist circumference. Results were corrected for multiple comparisons using a 5% false discovery rate. Result In both the AD (n = 73) and MCI (n = 28) groups, fatty acid epoxide concentrations were generally associated with higher FA. Diol concentrations were generally associated with lower FA in AD, but with higher FA in MCI. Epoxide concentrations were associated with greater MD in AD but with less MD in MCI. There were multiple associations between diols and greater regional BPF in AD that were less pronounced and less widespread in the MCI group; however the trend was consistent between AD and MCI for the left middle inferior frontal region (greater diols, greater BPF). In AD, it is notable that the 14(15) arachidonic acid epoxide was associated with lower WMH volumes (Spearman’s ρ: ‐0.234 to ‐0.577); the 9(10) linoleic acid epoxide was associated with greater temporal lobe BPF (Spearman’s ρ: 0.204 to 0.499). Conclusion Differential correlations between plasma oxylipin concentrations and regional neuroimaging measures between AD and MCI suggest that the involvement of the CYP450‐sEH pathway may differ across stages of AD progression.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".