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

Aliza P. Wingo, Eric B. Dammer, Michael S. Breen, Benjamin A. Logsdon, Duc M. Duong, Juan C. Troncosco, Madhav Thambisetty, Thomas G. Beach, Geidy E. Serrano, Eric M. Reiman, Richard John Caselli, James J. Lah, Nicholas T. Seyfried, Allan I. Levey, Thomas S. Wingo

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1619
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Proteomics
brain
Brain
Trajectories
trajectories
proteins
Proteins
proteome
Proteome
Meta-Analysis
hubs
apoptosis
pathology
Pathology
Apoptosis
Inflammation
Neuropathology

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Wingo, A. P., Dammer, E. B., Breen, M. S., Logsdon, B. A., Duong, D. M., Troncosco, J. C., ... Wingo, T. S. (2019). Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age. Nature communications, 10(1), [1619]. https://doi.org/10.1038/s41467-019-09613-z

Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age. / 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 John; Lah, James J.; Seyfried, Nicholas T.; Levey, Allan I.; Wingo, Thomas S.

In: Nature communications, Vol. 10, No. 1, 1619, 01.12.2019.

Research output: Contribution to journalArticle

Wingo, AP, Dammer, EB, Breen, MS, Logsdon, BA, Duong, DM, Troncosco, JC, Thambisetty, M, Beach, TG, Serrano, GE, Reiman, EM, Caselli, RJ, Lah, JJ, Seyfried, NT, Levey, AI & Wingo, TS 2019, 'Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age', Nature communications, vol. 10, no. 1, 1619. https://doi.org/10.1038/s41467-019-09613-z
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 John ; Lah, James J. ; Seyfried, Nicholas T. ; Levey, Allan I. ; Wingo, Thomas S. / Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age. In: Nature communications. 2019 ; Vol. 10, No. 1.
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