Unique CSF lipid signature in asymptomatic subjects with a parental history of Alzheimer’s disease and its association with key apolipoprotein species
Bibliographic record
Abstract
Abstract Background CSF apolipoproteins exhibit lipid‐specific relationships (signatures) with Alzheimer’s disease (AD) pathological markers and APOE‐ε4 in asymptomatic individuals. Method Mass spectrometry‐based CSF lipid analysis was performed as described before (Sampaio et al. 2011). Lipids were extracted using a one‐step chloroform/methanol procedure. After extraction, resulting samples were analyzed by direct infusion on a QExactive mass spectrometer equipped with a TriVersa NanoMate ion source. Both MS and MSMS data were combined to monitor CE, DAG and TAG ions as ammonium adducts; PC, PC O‐, as acetate adducts; and CL, PA, PE, PE O‐, PG and PI as deprotonated anions. CSF levels of amyloid beta (Aβ42), and total Tau (t‐Tau) were measured by enzyme‐linked immunosorbent assay (Fujirebio, Sweden) whereas apolipoproteins (AI, AII, B, CI, CII, CIII, D, E and J) concentrations were assessed using the Luminex/Biorad assays kit (10‐plex magneto‐fluorescent immunoassays, BioRad, USA). Results To characterize human CSF lipid signatures and their relationship to several apolipoproteins in pre‐symptomatic AD, we profiled and analyzed 21 classes of lipid species (for a total of 796 sub‐species) and 10 apolipoproteins in 120 cognitively unaffected subjects exhibiting various levels of total tau, p(181)tau and Aβ42. Figure 1 illustrates the signature profile (after FDR correction) following stratification by APOE‐ε4 genotype at the time of recruitment, when no cognitive deficit was detected. Please note the preferential associations between phosphatidylethanolamine acetate species and apoB levels in the CSF in non‐ε4 carrier. The apoD‐lipid signature profile was found to be very different in ε4 versus non‐ε4 carriers. Figure 2 illustrates the different associations between lipid species and the different apolipoproteins found in the CSF as a function of AD severity (stratified using the CSF T‐Tau/Aβ42 ratio). As ratio increases (top tertile) and pathology unfolds, the lipid signatures become markedly altered, with strong effects observed with apoB, apoD and apoJ interactions. Conclusion Our results suggest that early amyloid and tau pathologies modulate the release of specific lipid species in the CSF which alters their relationship with apolipoproteins in an APOE‐ε4‐dependent manner.
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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".