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    Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age

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    Author
    Wingo, Aliza P
    Dammer, Eric B
    Breen, Michael S
    Logsdon, Benjamin A
    Duong, Duc M
    Troncosco, Juan C
    Thambisetty, Madhav
    Beach, Thomas G
    Serrano, Geidy E
    Reiman, Eric M
    Caselli, Richard J
    Lah, James J
    Seyfried, Nicholas T
    Levey, Allan I
    Wingo, Thomas S
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    Affiliation
    Univ Arizona
    Issue Date
    2019-04-08
    
    Metadata
    Show full item record
    Publisher
    NATURE PUBLISHING GROUP
    Citation
    Wingo, 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.
    Journal
    NATURE COMMUNICATIONS
    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.
    Collection Information
    This 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.
    Abstract
    In 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.
    Note
    Open access journal
    ISSN
    2041-1723
    PubMed ID
    30962425
    DOI
    10.1038/s41467-019-09613-z
    Version
    Final published version
    Sponsors
    Accelerating 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]
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-019-09613-z
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