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

Autor: Amy P. Karns, Jonathan Aballi, Ibarra Arkaitz, Alexander D. Acosta, Donna M. Wilcock, Neeraj Salathia, Jiali Zhuang, James B. Brewer, Mike Nerenberg, Shusuke Toden, Stephen R. Quake
Rok vydání: 2020
Předmět:
Aging
Messenger
Brain tissue
Cell free
Disease
Neurodegenerative
Bioinformatics
Alzheimer's Disease
DNA sequencing
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Clinical Research
Genetics
Acquired Cognitive Impairment
Humans
Medicine
2.1 Biological and endogenous factors
RNA
Messenger
Aetiology
Gene
Research Articles
030304 developmental biology
0303 health sciences
Messenger RNA
Multidisciplinary
business.industry
Gene Expression Profiling
Neurosciences
SciAdv r-articles
Brain
High-Throughput Nucleotide Sequencing
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Pathophysiology
Patient management
Brain Disorders
Good Health and Well Being
Neurological
RNA
Dementia
business
Cell-Free Nucleic Acids
030217 neurology & neurosurgery
Research Article
Neuroscience
Zdroj: Science advances, vol 6, iss 50
Science Advances
Popis: Transcriptomic profiles of Alzheimer’s disease patients and healthy individuals were investigated using cell-free mRNA sequencing.
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.
Databáze: OpenAIRE
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