ArticlemedRxiv : the preprint server for health sciences2025
Effects of Non-Cardiac/Non-neurologic Surgery and Anaesthesia on the CSF Proteome, and Modulation by the APOE Mimetic Peptide CN-105.
Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03802396 (Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium and postopErative Cognitive Dysfunction), which is not on this map. Not yet cited in PubMed.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium and postopErative Cognitive Dysfunction (MARBLE): A Phase 2 Trial to Evaluate the Efficacy and Feasibility of CN-105 in Preventing Postoperative Cognitive Dysfunction and Delirium
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9 authors.
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Abstract
Objective: To evaluate the effect of non-cardiac/non-neurologic surgery on the CSF proteome, and the effect of the APOE mimetic peptide CN-105 on postoperative CSF proteome changes. Methods: We performed mass spectrometry-based proteomics on preoperative and 24 hour postoperative cerebrospinal fluid (CSF) samples from 137 patients (age>60) in the MARBLE trial (ct.gov identifier: NCT03802396), who were randomized to receive APOE mimetic peptide CN-105 (or placebo), and in an independent replication cohort. Linear regression was used to evaluate postoperative changes in CSF protein levels and pathway scores (measured by single-sample gene set enrichment analysis [ssGSEA]), with false discovery rate (FDR)-based multiple comparison correction. Results: Among 2,086 proteins, 881 (42.2%) showed a change after surgery (p-FDR<0.05), of which 57 proteins (6.4%) showed a log2 fold change >0.5 or <-0.5, and postoperative changes occurred in 1,001 (54.0%) of 1854 pathways (p-FDR<0.05). Similar temporal effects were seen in the majority of these proteins and pathways in the replication cohort. The 5 most significantly upregulated CSF pathways involved smooth muscle cell migration (and its regulation) or apoptotic signaling and regulation (including within endothelial cells). The 5 most significantly downregulated CSF pathways included non-canonical NF-κB signal transduction regulation, leukocyte apoptotic process (and negative regulation of it), and sulfur and proteoglycan metabolic processes. There was no significant CN-105 effect on 24-hour postoperative changes in CSF protein levels or ssGSEA pathway scores (p-FDR>0.05 for all). Conclusions: Significant postoperative changes occurred in over 40% of proteins and over 50% of pathways in the CSF, most significantly in smooth muscle, endothelial, leukocyte, and apoptosis pathways.
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