P3‐006: MINING THE NEURAL AND PLASMA PHOSPHOLIPIDOME TO IDENTIFY CRITICAL LIPID DETERMINANTS OF ALZHEIMER'S DISEASE CONVERSION
Bibliographic record
Abstract
Commonly conceptualized as undulating fields of identical molecules, neuronal membranes are, in fact, made up of hundreds of chemically and molecularly diverse lipid species. Here, we asked whether impairment of phosphocholine (PC) membrane can be used to predict transition from a pre-symptomatic to symptomatic state in (1) an experimental mouse model of familial Alzheimer's Disease (AD) and (2) in a clinical pilot study of mild cognitive impairment (MCI) and sporadic AD. The PC lipidome was profiled in hippocampus, temporal cortex, plasma at 2, 4, 6, and 8 months in the TgCRND8 AD mouse model and their NonTg littermates following assessment of learning and memory impairment in the Morris Water Maze. These results were compared to clinical circulating profiles of a pilot cohort of 21 cognitively normal, 17 mild cognitive impairment (MCI) patients, and 32 AD patients. Patients were assessed using the Clinical Dementia Rating (CDR), Structured Clinical Interview for DSM-IV Disorders - Depression scale (SCID-I), Hamilton Rating Scale for Depression [HAM-D], and Mini Mental State Examination (MMSE). PCs were isolated using a modified Bligh & Dyer method adapted for efficient extraction of phosphatidylcholines, alkyacylphosphocholines, plasmenylacylphosphocholines, and acylformylglycerophosphocholines. Profiling was performed by LC-ESI-MS with in both precursor ion mode (discovery) and multiple reaction monitoring mode (quantitation). 499 unique PC lipid species were identified. In NonTg mice, PCs clearly clustered into expected patterns of “stable” critical compositions, structural species being actively mobilized to maintain these critical compositions, and bioactive signaling molecules. The abundance of 24 PC species was significantly altered in 5.5 month old TgCRND8 mice. Significant correlations between the abundance of 13 species in either the hippocampus or temporal cortex were detected that could be predicted by associated changes in the circulating lipidome. Experimental profiles were then compared to clinical profiles as part of a pilot study. Increases in 3 critical species correlated with CDR and/or MMSE scores in MCI and AD and 4 species correlated with HAM-D scores in controls. These data provide proof of principle justifying a larger clinical investigation into the capacity of the circulating phospholipidome to predict disease 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 | 0.000 |
| 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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".