Aberrant glycerophosphocholine metabolism is a primary and targetable pathology in Alzheimer Disease
Bibliographic record
Abstract
Glycerophospholipids are often overlooked as immediate response elements yet they exert fundamental control over cell viability. They represent the major building blocks of biological membranes and modulate membrane trafficking. Enzymatic processing of choline‐containing membrane phospholipids by cytosolic phospholipase A2 (cPLA2) generates powerful smaller intracellular second messengers (~450–600 Da) as well as arachidonic acid and its metabolites. Individual isoforms control distinct cellular processes, but little is known about how they respond to normal brain functions and neurodegenerative disease state. Recent advances in mass spectrometry are enabling large‐scale profiling of individual lipid isoforms in brain tissue and cells. We capitalize on these advances to address the question whether aberrant membrane lipid metabolism is a risk factor for neurodegenerative disease. Here, we employed high performance liquid chromatography combined with electrospray ionization mass spectrometry (LC‐ESI‐MS) to profile glycerophosphocholine second messenger metabolism in the post‐mortem human entorhinal cortex and hippocampus, as well as in the temporal cortex and hippocampus of C57BL/6 × 129SV/J hybrid mice over the course of a 24 h period.
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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 | 0.001 | 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".