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dc.contributor.authorWingo, Aliza P
dc.contributor.authorDammer, Eric B
dc.contributor.authorBreen, Michael S
dc.contributor.authorLogsdon, Benjamin A
dc.contributor.authorDuong, Duc M
dc.contributor.authorTroncosco, Juan C
dc.contributor.authorThambisetty, Madhav
dc.contributor.authorBeach, Thomas G
dc.contributor.authorSerrano, Geidy E
dc.contributor.authorReiman, Eric M
dc.contributor.authorCaselli, Richard J
dc.contributor.authorLah, James J
dc.contributor.authorSeyfried, Nicholas T
dc.contributor.authorLevey, Allan I
dc.contributor.authorWingo, Thomas S
dc.date.accessioned2019-08-13T19:00:55Z
dc.date.available2019-08-13T19:00:55Z
dc.date.issued2019-04-08
dc.identifier.citationWingo, A. P., Dammer, E. B., Breen, M. S., Logsdon, B. A., Duong, D. M., Troncosco, J. C., ... & Caselli, R. J. (2019). Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age. Nature communications, 10(1), 1619.en_US
dc.identifier.issn2041-1723
dc.identifier.pmid30962425
dc.identifier.doi10.1038/s41467-019-09613-z
dc.identifier.urihttp://hdl.handle.net/10150/633809
dc.description.abstractIn advanced age, some individuals maintain a stable cognitive trajectory while others experience a rapid decline. Such variation in cognitive trajectory is only partially explained by traditional neurodegenerative pathologies. Hence, to identify new processes underlying variation in cognitive trajectory, we perform an unbiased proteome-wide association study of cognitive trajectory in a discovery (n = 104) and replication cohort (n = 39) of initially cognitively unimpaired, longitudinally assessed older-adult brain donors. We find 579 proteins associated with cognitive trajectory after meta-analysis. Notably, we present evidence for increased neuronal mitochondrial activities in cognitive stability regardless of the burden of traditional neuropathologies. Furthermore, we provide additional evidence for increased synaptic abundance and decreased inflammation and apoptosis in cognitive stability. Importantly, we nominate proteins associated with cognitive trajectory, particularly the 38 proteins that act independently of neuropathologies and are also hub proteins of protein co-expression networks, as promising targets for future mechanistic studies of cognitive trajectory.en_US
dc.description.sponsorshipAccelerating Medicine Partnership for AD [U01AG046161, U01 AG061357]; Emory Alzheimer's Disease Research Center [P50 AG025688]; NINDS Emory Neuroscience Core [P30 NS055077]; intramural program of the National Institute on Aging (NIA); Alzheimer's Association; Alzheimer's Research UK; Michael J. Fox Foundation for Parkinson's Research; Weston Brain Institute Biomarkers Across Neurodegenerative Diseases Grant [11060]; National Institute of Neurological Disorders and Stroke [U24 NS072026]; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]; [R01 AG056533]; [R01 AG053960]; [U01 MH115484]; [I01 BX003853]; [IK2 BX001820]; [R01 AG061800]; [R01 AG057911]en_US
dc.language.isoenen_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.rights© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.titleLarge-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced ageen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizonaen_US
dc.identifier.journalNATURE COMMUNICATIONSen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleNature communications
refterms.dateFOA2019-08-13T19:00:55Z


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