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Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study
Author(s) -
Picca Anna
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09413
Subject(s) - biology , parkinson's disease , cytochrome c oxidase , inflammation , protein subunit , neurodegeneration , mitochondrion , alpha synuclein , cd63 , microbiology and biotechnology , medicine , biochemistry , endocrinology , immunology , microvesicles , disease , gene , microrna
Systemic inflammation and mitochondrial dysfunction are involved in neurodegeneration in Parkinson’s disease (PD). Extracellular vesicle (EV) trafficking may link inflammation and mitochondrial dysfunction. In the present study, circulating small EVs (sEVs) from 16 older adults with PD and 12 controls were purified and characterized. A panel of circulating inflammatory biomolecules was measured by multiplex immunoassay. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers [adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), NADH:ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol‐cytochrome C reductase core protein 2 (UQCRC2)] were quantified by immunoblotting. Relative to controls, PD participants showed a greater amount of circulating sEVs. Levels of CD9 and CD63 were lower in the sEV fraction of PD participants, while those of CD81 were similar between groups. Lower levels of ATP5A, NDUFS3, and SDHB were detected in sEVs from PD participants. No signal was retrieved for UQCRC2, MTCOI, or NDUFB8 in either participant group. To identify a molecular signature in circulating sEVs in relationship to systemic inflammation, a low level‐fused (multi‐platform) partial least squares ‐ discriminant analysis was applied. The model correctly classified 94.2±6.1% PD participants and 66.7±5.4% controls, and identified as relevant seven biomolecules (CD9, NDUFS3, C‐reactive protein, fibroblast growth factor 21, interleukin 9, macrophage inflammatory protein 1b, and tumor necrosis factor alpha). In conclusion, a mitochondrial signature was identified in circulating sEVs from older adults with PD, in association with a specific inflammatory profile. In‐depth characterization of sEV trafficking may allow identifying new biomarkers for PD and possible targets for personalized interventions. Support or Funding Information Innovative Medicine Initiative‐Joint Undertaking (IMI‐JU #115621)