P3‐157: Indices of Plasmalogen Biosynthesis in ADNI‐1 Baseline Serum Samples: Association with Progression to Dementia in Subjects with Mild Cognitive Impairment
Bibliographic record
Abstract
Altered lipid metabolism has been implicated epidemiologically in risk for sporadic Alzheimer’s disease (AD); the underlying mechanisms remain uncertain. Although cholesterol and circulating lipoproteins have been the most well-studied lipids in AD, recent data implicate other classes such as glycerophospholipids (GPL). Plasmalogens (Pls), a GPL subclass, are integral membrane components with functions relevant to AD pathophysiology, including promoting vesicle fusion necessary for synaptic neurotransmitter release; modulation of membrane fluidity, raft dynamics, and antioxidant functions; and neuroprotection. Plasmalogen-rich membrane regions favor amyloid precursor protein (APP) breakdown by α-secretase to non-amyloidogenic products, over amyloidogenic β-secretase-mediated products that promote AD plaque formation. The initial steps of endogenous Pls synthesis require peroxisomes, notably in the liver. Peroxisomal function is decreased in older individuals; previous studies have shown decreased Pls in AD serum and postmortem brain. We measured Pls biosynthesis indices in ADNI-1 baseline serum vs. progression from MCI to AD. We measured 4 ethanolamine plasmalogens (PlsEtn) and 4 related phosphatidylethanolamines (PtdEtn) by flow-injection tandem mass spectrometry (FIA-MS/MS) in serum from 736 Alzheimer’s Disease Neuroimaging Initiative (ADNI-1) subjects that included 20 blinded technical replicates. We calculated 5 key ratios of PlsEtn species to each other and to corresponding PtdEtn reflecting Pls biosynthesis and peroxisomal beta-oxidation. Quality control analyses showed strong correlation between replicates (r>0.95, p<0.001) for all ratios. We then calculated an index of plasmalogen biosynthesis from the mean of 2 ratios (PlsEtn 22:6/PtdEtn 22:6, PlsEtn 20:5/PtdEtn 22:6), termed “PL/PE.” We examined the relationship between the PL/PE ratio and progression to AD in 358 patients with MCI at baseline, adjusting for age, gender, APOE genotype, body mass index, and concomitant medications. Higher baseline PL/PE was associated with a significantly (HR = 0.80, p<0.01) reduced risk of progression to AD in patients with MCI at baseline (Figure).
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 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".