Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles
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 diagnos...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.581882/full |
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| author | Kyoung Mi Kim Kyoung Mi Kim Qiong Meng Olivia Perez de Acha Maja Mustapic Aiwu Cheng Erden Eren Gautam Kundu Yulan Piao Rachel Munk William H. Wood Supriyo De Ji Heon Noh Michael Delannoy Lesley Cheng Kotb Abdelmohsen Dimitrios Kapogiannis Myriam Gorospe |
| author_facet | Kyoung Mi Kim Kyoung Mi Kim Qiong Meng Olivia Perez de Acha Maja Mustapic Aiwu Cheng Erden Eren Gautam Kundu Yulan Piao Rachel Munk William H. Wood Supriyo De Ji Heon Noh Michael Delannoy Lesley Cheng Kotb Abdelmohsen Dimitrios Kapogiannis Myriam Gorospe |
| author_sort | Kyoung Mi Kim |
| collection | DOAJ |
| description | 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 H2O2), 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. |
| first_indexed | 2024-12-13T17:55:05Z |
| format | Article |
| id | doaj.art-0b95c856d16740bc8b136009849272e1 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T17:55:05Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-0b95c856d16740bc8b136009849272e12022-12-21T23:36:24ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.581882581882Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular VesiclesKyoung Mi Kim0Kyoung Mi Kim1Qiong Meng2Olivia Perez de Acha3Maja Mustapic4Aiwu Cheng5Erden Eren6Gautam Kundu7Yulan Piao8Rachel Munk9William H. Wood10Supriyo De11Ji Heon Noh12Michael Delannoy13Lesley Cheng14Kotb Abdelmohsen15Dimitrios Kapogiannis16Myriam Gorospe17Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesDepartment of Biological Sciences, Chungnam National University, Daejeon, South KoreaLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesDepartment of Biochemistry, Chungnam National University, Daejeon, South KoreaDepartment of Cell Biology and Imaging Facility, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Biochemistry and Genetics, School of Molecular Science, La Trobe University, Melbourne, VI, AustraliaLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesLaboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United StatesAlzheimer’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 H2O2), 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.https://www.frontiersin.org/articles/10.3389/fcell.2020.581882/fullextracellular vesiclesAlzheimer’s diseasemitochondrial proteinmitochondrial RNAbiomarker |
| spellingShingle | Kyoung Mi Kim Kyoung Mi Kim Qiong Meng Olivia Perez de Acha Maja Mustapic Aiwu Cheng Erden Eren Gautam Kundu Yulan Piao Rachel Munk William H. Wood Supriyo De Ji Heon Noh Michael Delannoy Lesley Cheng Kotb Abdelmohsen Dimitrios Kapogiannis Myriam Gorospe Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles Frontiers in Cell and Developmental Biology extracellular vesicles Alzheimer’s disease mitochondrial protein mitochondrial RNA biomarker |
| title | Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles |
| title_full | Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles |
| title_fullStr | Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles |
| title_full_unstemmed | Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles |
| title_short | Mitochondrial RNA in Alzheimer’s Disease Circulating Extracellular Vesicles |
| title_sort | mitochondrial rna in alzheimer s disease circulating extracellular vesicles |
| topic | extracellular vesicles Alzheimer’s disease mitochondrial protein mitochondrial RNA biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.581882/full |
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