PROTEOME-WIDE ANALYSIS IDENTIFIES AND VALIDATES CHITINASE-3-LIKE PROTEIN 1 AS A RISK AND DISEASE MARKER OF DELIRIUM - Abstract citation igaf122.1052 - Findings on proteomics biomarkers

Sep 28, 2026

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Delirium, an acute change in cognition common among older adults, remains a clinical diagnosis without established biomarkers. A nested matched case-control analysis within the Successful Aging after Elective Surgery study assessed whether plasma protein levels before surgery and on postoperative day 2 associate with delirium and later consequences such as long-term cognitive decline and Alzheimer’s disease. Using SOMAscan and ELISA validation, the study tested 1305 proteins and identified CHI3L1/YKL-40 as the sole delirium-associated protein in both predictor models.

LanguageEnglish

CategoryHealthcare

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Abstract

Study design and proteomics approach

Biomarker identification and validation

Mechanistic interpretation and implications

312 Innovation in Aging, 2025, Vol. 9, No. S2 Abstract citation ID: igaf122.1052 PROTEOME-WIDE ANALYSIS IDENTIFIES AND VALIDATES CHITINASE-3-LIKE PROTEIN 1 AS A RISK AND DISEASE MARKER OF DELIRIUM Sarinnapha Vasunilashorn1, Simon Dillon1, Tamara Fong2, Long Ngo1, Hasan Otu3, Sharon Inouye4, Edward Marcantonio1, and Towia Libermann1, 1. Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States, 2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States, 3. University of NebraskaLincoln, Lincoln, Nebraska, United States, 4. Marcus Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts, United States Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel markers of risk and disease progression for postoperative delirium and its associated long-term consequences (eg, long-term cognitive decline and Alzheimer’s disease [AD]) . In a nested matched case-control study (18 delirium/no-delirium pairs) within the Successful Aging after Elective Surgery study (N = 556), we evaluated the association of 1305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to enzyme-linked immunosorbant assay (ELISA) validation data of one protein across the full cohort. Multi-protein modeling included delirium biomarkers identified in prior work (C-reactive protein, interleukin-6 [IL6]). We identified chitinase-3-like-protein-1 (CHI3L1/YKL-40) as the sole delirium-associated protein in both a PREOP and a POD2 predictor model, a finding confirmed by ELISA. Multi-protein modeling found high PREOP CHI3L1/YKL-40 and POD2 IL6 increased the risk of delirium (relative risk [95% confidence interval] Quartile [Q]4 vs Q1: 2.4[1.2-5.0] and 2.1[1.1-4.1], respectively) . Our identification of CHI3L1/YKL-40 in postoperative delirium parallels reports of CHI3L1/YKL-40 and its association with aging, mortality, and age-related conditions including AD onset and progression. This highlights the type 2 innate immune response, involving CHI3L1/YKL-40, as an underlying mechanism of postoperative delirium, a common, morbid, and costly syndrome that threatens the independence of older adults.

FAQs

Why are biomarkers important for delirium in older adults?

Delirium is a common, costly syndrome, but it is still diagnosed clinically because no established biomarkers guide diagnosis or management.

Which plasma proteins were evaluated and how were they measured?

The study evaluated 1305 plasma proteins preoperatively and on postoperative day 2 using SOMAscan, with enzyme-linked immunosorbant assay (ELISA) used for validation of a protein across the cohort.

What biomarker was identified as associated with postoperative delirium?

Chitinase-3-like-protein-1 (CHI3L1/YKL-40) was identified as the sole delirium-associated protein in both the PREOP and POD2 predictor models, and this finding was confirmed by ELISA.

Sep 28, 2026

Uploaded by Aria