Plasma proteome profile of Lewy body pathology‐positive individuals
Bibliographic record
Abstract
Abstract Background Lewy bodies (LB), the main hallmark of Parkinson’s disease (PD), are a frequent co‐pathology in Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). The varying extents of LB pathology in these disorders can influence disease progression and severity. Consequently, understanding LB impact on the proteomic profile of these diseases is crucial, potentially leading to identifyng novel blood biomarkers related to this pathology which are urgently needed. The aim of this project was to assess novel NULISAseq™ α‐synuclein (αSyn) biomarkers in blood. Considering the prevalence of monomeric αSyn in blood, we investigated whether other plasma proteins identified via NULISAseq™ or protein models could serve as surrogates for LB pathology determined by real‐time quake‐inducing conversion seed amplification assay (SAA). Method The proteomic profile of two independent cohorts was assessed using the NULISAseq™ CNS Disease Panel (Alamar Biosciences). A pilot cohort included amyloid‐β (Aβ)‐positive and SAA‐negative AD patients (n = 30) and Aβ‐negative SAA‐positive patients (DLB, n = 22; PD, n = 2). The TRIAD cohort included young (n = 32), cognitively unimpaired Aβ‐positive and Aβ‐negative (CU+, n = 111; CU‐, n = 26) individuals, Aβ‐positive and Aβ‐negative mild cognitive impairment (MCI+, n = 40; MCI‐, n = 39), as well as AD dementia (ADD, n = 38) and non‐AD (n = 27) patients. LB pathology was confirmed in both cohorts by the same SAA method. Result In the pilot cohort, no differences in plasma αSyn (SNCA, pSyn129, Oligo‐Syn) levels were observed. However, plasma phosphorylated tau‐217 (pTau‐217, logFoldChange (FC) = ‐1.00, p.adj<0.001), enolase‐2 (ENO2, logFC = ‐2.03, p.adj = 0.02), Fms Related Receptor Tyrosine Kinase 1 (FLT1, logFC = 0.54, p.adj = 0.04), and amyloid‐β42 (Aβ42, logFC = 1.09, p.adj = 0.04) were differentially expressed in SAA‐negative vs SAA‐positive patients. Furthermore, the ratio of pTau‐217/FLT1 exhibited the best separation between the SAA‐positive and SAA‐negative groups (AUC = 0.90, 95% CI 0.82‐0.98). The TRIAD cohort was used to validate these results, from which data is to be shown. Conclusion The proteomic profile of LB‐positive is distinct from LB‐negative individuals, with four biomarkers differentially expressed in plasma. We also determined that a combination of these biomarkers may be useful to discriminate SAA‐positive from SAA‐negative individuals. Plasma αSyn levels did not reflect CSF SAA outcome, possibly due to peripheral αSyn expression not reflecting brain pathology.
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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 | 0.000 | 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".