F3‐02‐04: SERUM INDICES OF ETHANOLAMINE PLASMALOGENS AND PHOSPHATIDE METABOLISM IN THE COMBINED ADNI‐1/GO/2 COHORT: DOES THE LIVER CONTRIBUTE TO AD RISK BY FAILING TO SUPPLY KEY LIPIDS TO THE BRAIN?
Bibliographic record
Abstract
Altered lipid metabolism is linked to Alzheimer's disease (AD) risk; the underlying mechanisms are incompletely understood. The liver synthesizes many circulating lipids and lipoproteins; some are critical for supporting neuronal and brain functions. For example, the ether lipid plasmalogens promote vesicle fusion and thus synaptic function, are membrane antioxidants, and affect other AD-relevant processes. The liver is a key site for plasmalogen synthesis, remodeling, and incorporation into circulating lipoproteins, some of which can enter the brain. Liver peroxisomal activity is crucial for plasmalogen synthesis; a deficiency can limit delivery to brain, disrupt synaptic function, and impair cognition. Our consortium is engaged in further exploration of these and other lipids and their relation to liver-related genes and proteins that may influence brain function via circulating lipoproteins. We measured 8 phosphoethanolamines (PEs), including 4 ethanolamine plasmalogens and 4 closely-related phosphatidylethanolamines, in >1500 baseline serum specimens from Alzheimer's Disease Neuroimaging Initiative (ADNI)-1,-GO, and -2 cohorts. We derived 4 indices: PL-PX (ethanolamine plasmalogen remodeling); PE-PX (phosphatidylethanolamine remodeling); PL/PE (ethanolamine plasmalogen/phosphatide ratios); and PBV (a composite index). We tested for cross-sectional associations of these indices with cognition by ADAS-Cog13 (in ADNI) and MMSE, and diagnosis (AD vs. (L)MCI vs. cognitively normal (CN)). We observed significant negative associations of baseline ADAS-Cog13 score with PL-PX (coeff.= -0.135/p=3.24E-6/q=1.94E-5) and overall PBV (coeff.= -0.130/p=6.92E-5), and for MMSE with PL-PX (coeff.= 0.040/p=1.28E-9) and PBV (coeff.= 0.038/p=6.50E-9). Logistic regression models showed statistically-significant negative relationships of AD vs. CN diagnosis with PL-PX (coeff.= -0.244/p=0.007) and overall PBV (coeff.= -0.255/p=0.005), i.e., lower values of these indices associated with a higher likelihood of AD, and a similar pattern of LMCI vs. CN diagnosis associations with PL-PX (coeff.= -0.330/p=2.89E-5) and PBV (coeff.= -0.294, p=1.99E-4). These data provide further evidence that altered ethanolamine plasmalogen metabolism contribute to the risk of cognitive impairment in AD and MCI. Failure of plasmalogen synthesis involving liver peroxisomes may adversely affect CNS synaptic and antioxidant functions and contribute to cognitive decline in AD. We are now further examining the connections between plasmalogens and other lipids vs. cognition, associations with gene expression in liver and brain, and network modeling approaches.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".