TY - JOUR
T1 - Noninvasive characterization of Alzheimer’s disease by circulating, cell-free messenger RNA next-generation sequencing
AU - Toden, Shusuke
AU - Zhuang, Jiali
AU - Acosta, Alexander D.
AU - Karns, Amy P.
AU - Salathia, Neeraj S.
AU - Brewer, James B.
AU - Wilcock, Donna M.
AU - Aballi, Jonathan
AU - Nerenberg, Mike
AU - Quake, Stephen R.
AU - Ibarra, Arkaitz
N1 - Publisher Copyright:
Copyright © 2020 The Authors,
PY - 2020/12/9
Y1 - 2020/12/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097806832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097806832&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abb1654
DO - 10.1126/sciadv.abb1654
M3 - Article
C2 - 33298436
AN - SCOPUS:85097806832
VL - 6
JO - Science advances
JF - Science advances
IS - 50
M1 - eabb1654
ER -