Noninvasive characterization of Alzheimer’s disease by circulating, cell-free messenger RNA next-generation sequencing

Shusuke Toden, Jiali Zhuang, Alexander D. Acosta, Amy P. Karns, Neeraj S. Salathia, James B. Brewer, Donna M. Wilcock, Jonathan Aballi, Mike Nerenberg, Stephen R. Quake, Arkaitz Ibarra

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The lack of accessible noninvasive tools to examine the molecular alterations occurring in the brain limits our understanding of the causes and progression of Alzheimer’s disease (AD), as well as the identification of effective therapeutic strategies. Here, we conducted a comprehensive profiling of circulating, cell-free messenger RNA (cf-mRNA) in plasma of 126 patients with AD and 116 healthy controls of similar age. We identified 2591 dysregulated genes in the cf-mRNA of patients with AD, which are enriched in biological processes well known to be associated with AD. Dysregulated genes included brain-specific genes and resembled those identified to be dysregulated in postmortem AD brain tissue. Furthermore, we identified disease-relevant circulating gene transcripts that correlated with the severity of cognitive impairment. These data highlight the potential of high-throughput cf-mRNA sequencing to evaluate AD-related pathophysiological alterations in the brain, leading to precision healthcare solutions that could improve AD patient management.

Original languageEnglish
Article numbereabb1654
JournalScience advances
Volume6
Issue number50
DOIs
StatePublished - Dec 9 2020

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Copyright © 2020 The Authors,

ASJC Scopus subject areas

  • General

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