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

10 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

Bibliographical note

Funding Information:
We thank R. Rava, G. Elias, T. Wright, J. Sninsky, and T. Maddala for conceptual discussions and critical reading of the manuscript. This publication was made possible thanks to funding from the bgC3 foundation. We also thank our collaborators at University of Washington in St. Louis and their grants [Healthy Aging and Senile Dementia (P01 AG03991), Alzheimer’s Disease Research Center (P50 AG05681), and Adult Children Study (P01 AG026276)]. We thank our collaborators from Indiana University for providing samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG021886) awarded by the National Institute on Aging [NIA and grant number U01 AT000162 from the National Center for Complementary and Alternative Medicine (NIH)]. We thank our collaborators at University of California, San Diego and collaborators from University of Kentucky (NIH grant number P30 AG028383).

Publisher Copyright:
Copyright © 2020 The Authors,

ASJC Scopus subject areas

  • General

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