Missorting of plasma miRNAs in aging and Alzheimer's disease

Maria Čarna, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jan S. Novotny, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Neda Dragišić, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Hanuš Slavik, Institute for Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
Kateřina Sheardova, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Yonas E. Geda, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA.Follow
Martin Vyhnalek, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jan Laczo, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jakub Hort, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Zixu Mao, Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
Robert A. Rissman, Department of Neurosciences, University of California San Diego, La Jolla, California, USA.
Marian Hajduch, Institute for Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
Eric B. Dammer, Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Gorazd B. Stokin, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.

Document Type

Article

Abstract

The observation that aging is regulated by microRNAs (miRNA) and at the same time represents the greatest risk factor for Alzheimer's disease (AD), prompted us to examine the circulating miRNA network in AD beyond aging. We here show that plasma miRNAs in aging are downregulated and predicted to be preferentially targeted to the extracellular vesicle (EV) content. In AD, miRNAs are further downregulated, display altered proportions of motifs relevant to their loading into EVs and secretion propensity, and are forecast to be found exclusively in EVs. The circulating miRNA network in AD, therefore, reflects pathological exacerbation of the aging process whereby physiological suppression of AD pathology by miRNAs becomes insufficient.

Medical Subject Headings

Humans; MicroRNAs (genetics); Alzheimer Disease (genetics); Extracellular Vesicles; Aging (genetics)

Publication Date

4-1-2023

Publication Title

Journal of neurochemistry

E-ISSN

1471-4159

Volume

165

Issue

2

First Page

149

Last Page

161

PubMed ID

36892419

Digital Object Identifier (DOI)

10.1111/jnc.15801

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