Authors: Zou, Haotian et al.
Preprint on medRxiv, October 2025. DOI: 10.1101/2025.10.06.25337433
This preprint reports findings from a proteomic analysis of cerebrospinal fluid (CSF) in older adults undergoing non-cardiac, non-neurologic surgery, focusing on how surgery alters the CSF proteome and whether the APOE-mimetic peptide CN-105 modifies these changes. The study analyzed paired pre- and 24-hour postoperative CSF samples from 137 participants in the MARBLE randomized trial and validated results in an independent cohort.
Of 2,086 measured proteins, 42% changed significantly after surgery, with 6% showing marked fold changes (> 0.5 or < –0.5). More than half of the 1,854 analyzed pathways were altered postoperatively, notably those linked to smooth muscle cell migration, endothelial apoptosis, and leukocyte signaling. The data suggest a robust neuroinflammatory and vascular response within 24 hours of surgery. Importantly, CN-105 showed no measurable effect on these proteomic alterations.
The authors conclude that surgery alone induces widespread CSF proteome shifts, especially in pathways related to vascular integrity and immune activation, and that the APOE-mimetic intervention did not mitigate these changes.
What You Should Know
• Major non-neurologic surgery triggers large-scale CSF proteomic alterations in older adults.
• The most affected pathways involve smooth muscle, endothelial, and immune cell regulation.
• The APOE-mimetic peptide CN-105 did not significantly influence early postoperative CSF protein or pathway changes.
• These findings highlight surgery’s broad impact on neurovascular and inflammatory biology but remain preliminary pending peer review.
(Note: This article is a preprint, meaning it has not yet undergone peer review. Peer review is the process where other independent experts evaluate a study’s methods, data, and conclusions before publication in a scientific journal. Until then, results should be interpreted as provisional and not used to guide clinical care.)