Missorting of plasma miRNAs in aging and Alzheimer's disease

Maria Čarna; Jan S. Novotny; Neda Dragišić; Hanuš Slavik; Kateřina Sheardova; Yonas E. Geda; Martin Vyhnalek; Jan Laczo; Jakub Hort; Zixu Mao; Robert A. Rissman; Marian Hajduch; Eric B. Dammer; Gorazd B. Stokin

doi:10.1111/jnc.15801

Missorting of plasma miRNAs in aging and Alzheimer's disease

Maria Čarna, Jan S. Novotny, Neda Dragišić, Hanuš Slavik, Kateřina Sheardova, Yonas E. Geda, Martin Vyhnalek, Jan Laczo, Jakub Hort, Zixu Mao, Robert A. Rissman, Marian Hajduch, Eric B. Dammer, Gorazd B. Stokin

Research output: Contribution to journal › Article › peer-review

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. (Figure presented.)

Original language	English (US)
Pages (from-to)	149-161
Number of pages	13
Journal	Journal of Neurochemistry
Volume	165
Issue number	2
DOIs	https://doi.org/10.1111/jnc.15801
State	Published - Apr 2023
Externally published	Yes

Keywords

Alzheimer's disease
aging
endosomes
extracellular vesicles
miRNA
ncRNA
plasma
short sequence motifs

ASJC Scopus subject areas

Biochemistry
Cellular and Molecular Neuroscience

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10.1111/jnc.15801

Cite this

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title = "Missorting of plasma miRNAs in aging and Alzheimer's disease",

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. (Figure presented.)",

keywords = "Alzheimer's disease, aging, endosomes, extracellular vesicles, miRNA, ncRNA, plasma, short sequence motifs",

author = "Maria {\v C}arna and Novotny, {Jan S.} and Neda Dragi{\v s}i{\'c} and Hanu{\v s} Slavik and Kate{\v r}ina Sheardova and Geda, {Yonas E.} and Martin Vyhnalek and Jan Laczo and Jakub Hort and Zixu Mao and Rissman, {Robert A.} and Marian Hajduch and Dammer, {Eric B.} and Stokin, {Gorazd B.}",

note = "Funding Information: This study was supported by the European Regional Development Fund No. CZ.02.1.01/0.0/0.0/16_019/0000868 ENOCH (G.B.S.), No. CZ.02.1.01/0.0/0.0/15_003/0000492 MAGNET (G.B.S.), the R01NS095269 (Z.M.), and P30‐AGO62429 (R.A.R.) grants. Publisher Copyright: {\textcopyright} 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.",

year = "2023",

month = apr,

doi = "10.1111/jnc.15801",

language = "English (US)",

volume = "165",

pages = "149--161",

journal = "Journal of Neurochemistry",

issn = "0022-3042",

publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Missorting of plasma miRNAs in aging and Alzheimer's disease

AU - Čarna, Maria

AU - Novotny, Jan S.

AU - Dragišić, Neda

AU - Slavik, Hanuš

AU - Sheardova, Kateřina

AU - Geda, Yonas E.

AU - Vyhnalek, Martin

AU - Laczo, Jan

AU - Hort, Jakub

AU - Mao, Zixu

AU - Rissman, Robert A.

AU - Hajduch, Marian

AU - Dammer, Eric B.

AU - Stokin, Gorazd B.

N1 - Funding Information: This study was supported by the European Regional Development Fund No. CZ.02.1.01/0.0/0.0/16_019/0000868 ENOCH (G.B.S.), No. CZ.02.1.01/0.0/0.0/15_003/0000492 MAGNET (G.B.S.), the R01NS095269 (Z.M.), and P30‐AGO62429 (R.A.R.) grants. Publisher Copyright: © 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

PY - 2023/4

Y1 - 2023/4

N2 - 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. (Figure presented.)

AB - 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. (Figure presented.)

KW - Alzheimer's disease

KW - aging

KW - endosomes

KW - extracellular vesicles

KW - miRNA

KW - ncRNA

KW - plasma

KW - short sequence motifs

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Missorting of plasma miRNAs in aging and Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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