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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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 J Caselli, James J Lah, Nicholas T Seyfried, Allan I Levey, Thomas S Wingo

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. More... »

PAGES

1619

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09613-z

DOI

http://dx.doi.org/10.1038/s41467-019-09613-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113300647

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30962425


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