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 | BackgroundPostoperative 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.ObjectiveTo utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD.MethodsUnbiased 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.ResultsMass 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).ConclusionThese 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 | ||
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 |
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