%0 Journal Article %J J Alzheimers Dis %D 2021 %T Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction. %A VanDusen, Keith W %A Li, Yi-Ju %A Cai, Victor %A Hall, Ashley %A Hiles, Sarah %A Thompson, J Will %A Moseley, M Arthur %A Cooter, Mary %A Acker, Leah %A Levy, Jerrold H %A Ghadimi, Kamrouz %A Quiñones, Quintin J %A Devinney, Michael J %A Chung, Stacey %A Terrando, Niccolò %A Moretti, Eugene W %A Browndyke, Jeffrey N %A Mathew, Joseph P %A Berger, Miles %X

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 withoutPOCD (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.

%B J Alzheimers Dis %V 80 %P 1281-1297 %8 2021 Apr 06 %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/33682719?dopt=Abstract %R 10.3233/JAD-201544