Mitochondrial RNA in Alzheimer's Disease Circulating Extracellular Vesicles.

Autor: Kim KM; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States.; Department of Biological Sciences, Chungnam National University, Daejeon, South Korea., Meng Q; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Perez de Acha O; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Mustapic M; Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Cheng A; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Eren E; Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Kundu G; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Piao Y; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Munk R; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Wood WH 3rd; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., De S; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Noh JH; Department of Biochemistry, Chungnam National University, Daejeon, South Korea., Delannoy M; Department of Cell Biology and Imaging Facility, Johns Hopkins University School of Medicine, Baltimore, MD, United States., Cheng L; Department of Biochemistry and Genetics, School of Molecular Science, La Trobe University, Melbourne, VI, Australia., Abdelmohsen K; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Kapogiannis D; Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States., Gorospe M; Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States.
Jazyk: angličtina
Zdroj: Frontiers in cell and developmental biology [Front Cell Dev Biol] 2020 Nov 16; Vol. 8, pp. 581882. Date of Electronic Publication: 2020 Nov 16 (Print Publication: 2020).
DOI: 10.3389/fcell.2020.581882
Abstrakt: Alzheimer's disease (AD) is the most common type of dementia. Amyloid β (Aβ) plaques, tau-containing neurofibrillary tangles, and neuronal loss leading to brain atrophy are pathologic hallmarks of AD. Given the importance of early diagnosis, extensive efforts have been undertaken to identify diagnostic and prognostic biomarkers for AD. Circulating extracellular vesicles (EVs) provide a platform for "liquid biopsy" biomarkers for AD. Here, we characterized the RNA contents of plasma EVs of age-matched individuals who were cognitively normal (healthy controls (HC)) or had mild cognitive impairment (MCI) due to AD or had mild AD dementia (AD). Using RNA sequencing analysis, we found that mitochondrial (mt)-RNAs, including MT-ND1-6 mRNAs and other protein-coding and non-coding mt-RNAs, were strikingly elevated in plasma EVs of MCI and AD individuals compared with HC. EVs secreted from cultured astrocytes, microglia, and neurons after exposure to toxic conditions relevant to AD pathogenesis (Aβ aggregates and H 2 O 2 ), contained mitochondrial structures (detected by electron microscopy) and mitochondrial RNA and protein. We propose that in the AD brain, toxicity-causing mitochondrial damage results in the packaging of mitochondrial components for export in EVs and further propose that mt-RNAs in plasma EVs can be diagnostic and prognostic biomarkers for MCI and AD.
(Copyright © 2020 Kim, Meng, Perez de Acha, Mustapic, Cheng, Eren, Kundu, Piao, Munk, Wood, De, Noh, Delannoy, Cheng, Abdelmohsen, Kapogiannis and Gorospe.)
Databáze: MEDLINE
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