期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 80, 期 3, 页码 1281-1297出版社
IOS PRESS
DOI: 10.3233/JAD-201544
关键词
Inflammation; mass spectrometry; neurocognitive disorders; postoperative cognitive dysfunction; proteomics
资金
- Duke Anesthesiology DREAM Innovation Grant
- NIH [R03 AG050918, T32GM008600, K76AG057022, P30AG028716, UH3AG056925]
- International Anesthesia Research Society
- Duke Anesthesiology Department
In this study, unbiased mass spectrometry was used to identify potential neuroinflammatory pathways underlying POCD, with results demonstrating changes in complement and coagulation pathways in the CSF of POCD patients.
Background: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD. Objective: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD. Methods: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis. Results: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in >50% of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus without POCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10(-13)). Conclusion: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.
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