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Missorting of plasma miRNAs in aging and Alzheimer's disease

M. Čarna, JS. Novotny, N. Dragišić, H. Slavik, K. Sheardova, YE. Geda, M. Vyhnalek, J. Laczo, J. Hort, Z. Mao, RA. Rissman, M. Hajduch, EB. Dammer, GB. Stokin

. 2023 ; 165 (2) : 149-161. [pub] 20230327

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc23010536

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.

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$a The observation that aging is regulated by microRNAs (miRNA) and at the same time represents the greatest risk factor for Alzheimer's disease (AD), prompted us to examine the circulating miRNA network in AD beyond aging. We here show that plasma miRNAs in aging are downregulated and predicted to be preferentially targeted to the extracellular vesicle (EV) content. In AD, miRNAs are further downregulated, display altered proportions of motifs relevant to their loading into EVs and secretion propensity, and are forecast to be found exclusively in EVs. The circulating miRNA network in AD, therefore, reflects pathological exacerbation of the aging process whereby physiological suppression of AD pathology by miRNAs becomes insufficient.
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$a Geda, Yonas E $u Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA $1 https://orcid.org/0000000311877230
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$a Laczo, Jan $u International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic $u Memory Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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