Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.

dc.contributor.author

VanDusen, Keith W

dc.contributor.author

Li, Yi-Ju

dc.contributor.author

Cai, Victor

dc.contributor.author

Hall, Ashley

dc.contributor.author

Hiles, Sarah

dc.contributor.author

Thompson, J Will

dc.contributor.author

Moseley, M Arthur

dc.contributor.author

Cooter, Mary

dc.contributor.author

Acker, Leah

dc.contributor.author

Levy, Jerrold H

dc.contributor.author

Ghadimi, Kamrouz

dc.contributor.author

Quiñones, Quintin J

dc.contributor.author

Devinney, Michael J

dc.contributor.author

Chung, Stacey

dc.contributor.author

Terrando, Niccolò

dc.contributor.author

Moretti, Eugene W

dc.contributor.author

Browndyke, Jeffrey N

dc.contributor.author

Mathew, Joseph P

dc.contributor.author

Berger, Miles

dc.contributor.author

MADCO-PC Investigators

dc.date.accessioned

2021-04-01T21:50:49Z

dc.date.available

2021-04-01T21:50:49Z

dc.date.issued

2021-02-26

dc.date.updated

2021-04-01T21:50:48Z

dc.description.abstract

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.
dc.identifier

JAD201544

dc.identifier.issn

1387-2877

dc.identifier.issn

1875-8908

dc.identifier.uri

https://hdl.handle.net/10161/22516

dc.language

eng

dc.publisher

IOS Press

dc.relation.ispartof

Journal of Alzheimer's disease : JAD

dc.relation.isversionof

10.3233/jad-201544

dc.subject

MADCO-PC Investigators

dc.title

Cerebrospinal Fluid Proteome Changes in Older Non-Cardiac Surgical Patients with Postoperative Cognitive Dysfunction.

dc.type

Journal article

duke.contributor.orcid

Li, Yi-Ju|0000-0001-6996-4834

duke.contributor.orcid

Acker, Leah|0000-0002-5534-6020

duke.contributor.orcid

Levy, Jerrold H|0000-0003-3766-4962

duke.contributor.orcid

Ghadimi, Kamrouz|0000-0002-9287-7541

duke.contributor.orcid

Devinney, Michael J|0000-0003-3906-6421

duke.contributor.orcid

Terrando, Niccolò|0000-0003-1803-5853

duke.contributor.orcid

Browndyke, Jeffrey N|0000-0002-8573-7073

duke.contributor.orcid

Mathew, Joseph P|0000-0002-3815-4131

duke.contributor.orcid

Berger, Miles|0000-0002-2386-5061

pubs.begin-page

1

pubs.end-page

17

pubs.organisational-group

School of Medicine

pubs.organisational-group

Duke-UNC Center for Brain Imaging and Analysis

pubs.organisational-group

Center for the Study of Aging and Human Development

pubs.organisational-group

Duke Institute for Brain Sciences

pubs.organisational-group

Surgery, Cardiovascular and Thoracic Surgery

pubs.organisational-group

Psychiatry & Behavioral Sciences, Geriatric Behavioral Health

pubs.organisational-group

Duke

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

University Institutes and Centers

pubs.organisational-group

Institutes and Provost's Academic Units

pubs.organisational-group

Surgery

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Psychiatry & Behavioral Sciences

pubs.organisational-group

Duke Innovation & Entrepreneurship

pubs.organisational-group

Anesthesiology, Cardiothoracic

pubs.organisational-group

Initiatives

pubs.organisational-group

Anesthesiology

pubs.organisational-group

Duke Science & Society

pubs.organisational-group

Anesthesiology, Neuroanesthesia

pubs.organisational-group

Cell Biology

pubs.organisational-group

Basic Science Departments

pubs.publication-status

Published

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
CSF Proteomics Manuscript 1-10-2021 (002).pdf
Size:
571.55 KB
Format:
Adobe Portable Document Format
Description:
Accepted version