Proteome-Wide Analysis Using SOMAscan Identifies and Validates Chitinase-3-Like Protein 1 as a Risk and Disease Marker of Delirium among Older Adults Undergoing Major Elective Surgery

Sarinnapha M. Vasunilashorn, Simon T. Dillon, Noel Y. Chan, Tamara G. Fong, Marie Joseph, Bridget Tripp, Zhongcong Xie, Long H. Ngo, Chun Geun Lee, Jack A. Elias, Hasan H. Otu, Sharon K. Inouye, Edward R. Marcantonio, Towia A. Libermann

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: 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]). Methods: 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]). Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)484-493
Number of pages10
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume77
Issue number3
DOIs
StatePublished - Mar 1 2022

Keywords

  • Inflammation
  • Postoperative
  • Proteomics

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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