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
Open Access
- 4 February 2021
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences
- Vol. 77 (3), 484-493
- https://doi.org/10.1093/gerona/glaa326
Abstract
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.Keywords
Funding Information
- National Institute on Aging (R01AG051658, P01AG031720, K01AG057836, R03AG061582, R24AG054259, R21AG057955, R01AG041274, R21AG048600, K24AG035075)
- Alzheimer’s Association
This publication has 45 references indexed in Scilit:
- Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort studyBrain, 2012
- Cognitive Trajectories after Postoperative DeliriumThe New England Journal of Medicine, 2012
- The Importance of Delirium: Economic and Societal CostsJournal of the American Geriatrics Society, 2011
- YKL-40 Expression in Traumatic Brain Injury: An Initial AnalysisJournal of Neurotrauma, 2010
- Development of a unidimensional composite measure of neuropsychological functioning in older cardiac surgery patients with good measurement precisionJournal of Clinical and Experimental Neuropsychology, 2010
- Delirium as a predictor of sepsis in post-coronary artery bypass grafting patients: a retrospective cohort studyCritical Care, 2010
- Delirium accelerates cognitive decline in Alzheimer diseaseNeurology, 2009
- Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosisThe Journal of Experimental Medicine, 2009
- High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortalityClinical and Experimental Immunology, 2007
- A comparison of methods for multiclass support vector machinesIEEE Transactions on Neural Networks, 2002