Authors: Yu et al.
The Daily Dose, IARS, Friday, May 8, 2026
Perioperative Effects of CN-105 Treatment on the Cerebrospinal Fluid Proteome
Key Points
Connie T. Yu, BS, received the Kosaka Top Scholars Abstract Award for research on CN-105 and perioperative changes in the cerebrospinal fluid proteome.
CN-105 is an APOE mimetic peptide being studied for its potential role in modulating neuroinflammatory pathways related to postoperative delirium.
The study found that CN-105 was associated with distinct perioperative changes in CSF proteins involved in inflammation, vascular signaling, and neuronal structure.
Many pro-inflammatory proteins showed reduced upregulation with CN-105 treatment, suggesting a biologically plausible anti-inflammatory mechanism.
The research may help identify molecular pathways, biomarkers, and future therapeutic targets for postoperative delirium.
Summary
This IARS Daily Dose article featured Connie T. Yu, BS, a first-year medical student at Tufts University School of Medicine and recipient of the 2026 Kosaka Top Scholars Abstract Award. Her award-winning abstract, “Perioperative Effects of CN-105 Treatment on the Cerebrospinal Fluid Proteome,” focuses on how CN-105 may affect neuroinflammatory processes in the human central nervous system during the perioperative period.
Ms. Yu’s interest in postoperative delirium began through her clinical experience as a nursing assistant caring for patients undergoing thoracic surgery and lung transplantation. In that role, she saw how common postoperative delirium can be and how significantly it affects both patients and families. Her background in biopsychology and neuroscience helped draw her toward the APOE pathway as a biologically grounded approach to understanding delirium risk.
The article explains that Ms. Yu later joined the research program of Miles Berger, MD, PhD, a neuro-anesthesiologist and translational human neuroscientist. Dr. Berger’s work focuses on mechanisms of perioperative neurocognitive disorders in older adults, including delirium. Through this collaboration, Ms. Yu contributed to research examining CN-105, an APOE mimetic peptide, and its effect on the cerebrospinal fluid proteome.
The central question of the research is how CN-105 modulates perioperative neuroinflammatory processes in the human central nervous system and whether these molecular changes may help explain its possible effects on postoperative delirium. This is important because postoperative delirium remains complex, common, and difficult to treat, especially in older adults and medically vulnerable surgical patients.
The study found that CN-105 was associated with distinct perioperative changes in CSF proteins. These changes involved proteins related to inflammation, vascular signaling, and neuronal structure. Notably, many pro-inflammatory proteins showed attenuated upregulation with treatment, which supports a plausible anti-inflammatory mechanism for CN-105.
This work is especially relevant because the APOE ε4 allele has long been associated with increased risk of Alzheimer’s disease and postoperative delirium. Despite that association, there are still no FDA-approved therapies that directly target this pathway. CN-105 was developed to address this gap, and this study helps connect clinical delirium outcomes with underlying biological pathways in the central nervous system.
The article emphasizes that the research may help bridge the gap between bedside observations and molecular mechanisms. By identifying CSF protein changes linked to treatment, investigators may be able to better understand which inflammatory and neuronal pathways contribute to postoperative delirium. This could eventually support biomarker development, risk stratification, and targeted therapeutic approaches.
The next steps include linking the observed proteomic changes more directly to delirium outcomes, characterizing the functional pathways behind the protein changes, validating the findings in larger cohorts, and exploring future Phase III trials. The research team also hopes to use this approach to identify biomarkers that could help predict risk and guide treatment response.
Ms. Yu described receiving the Kosaka Top Scholars Abstract Award as a major honor, especially as a first-year medical student. She credited the recognition to the mentorship and support of Dr. Miles Berger, the Berger Lab, the Stanford perioperative research team, Dr. Charlotte Herber, Duke University collaborators, the MARBLE study team, and the patients who participated in the MARBLE trial.
What You Should Know
This article highlights an important translational research effort in perioperative brain health. Postoperative delirium remains one of the most challenging complications in older surgical patients, and current treatment options are limited. By studying CN-105 and its effects on the CSF proteome, researchers are trying to identify the biological pathways that may drive delirium and cognitive vulnerability.
For anesthesia providers, the key takeaway is that delirium research is moving toward more precise molecular and biomarker-based approaches. Instead of treating delirium only after it appears, future strategies may involve identifying high-risk patients before symptoms develop and targeting specific inflammatory or neuroprotective pathways.
CN-105 is still investigational in this context, but the findings suggest that the APOE pathway may be a promising target for future therapy. If larger studies confirm these results, this line of research could help move perioperative delirium care from supportive management toward prediction, prevention, and targeted treatment.
Overall, the article shows how early-career investigators are helping advance anesthesiology research by connecting clinical outcomes with molecular mechanisms. Understanding how perioperative treatments change the central nervous system proteome may eventually improve recovery and quality of life for vulnerable surgical patients.
Thank you to IARS and The Daily Dose for allowing us to summarize and share this article.