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Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults

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dc.contributor.authorMendes-Silva, Ana Paula
dc.contributor.authorNikolova, Yuliya S.
dc.contributor.authorRajji, Tarek K.
dc.contributor.authorKennedy, James
dc.contributor.authorDiniz, Breno
dc.contributor.authorGonçalves, Vanessa F.
dc.contributor.authorVieira, Erica
dc.date.accessioned2024-10-22T17:25:31Z
dc.date.available2024-10-22T17:25:31Z
dc.date.issued2024-06
dc.description.abstractBackground: Disrupted cellular communication, inflammatory responses and mitochondrial dysfunction are consistently observed in late-life depression (LLD). Exosomes (EXs) mediate cellular communication by transporting molecules, including mitochondrial DNA (EX-mtDNA), playing critical role in immunoregulation alongside tumor necrosis factor (TNF). Changes in EX-mtDNA are indicators of impaired mitochondrial function and might increase vulnerability to adverse health outcomes. Our study examined EX-mtDNA levels and integrity, exploring their associations with levels of TNF receptors I and II (TNFRI and TNFRII), and clinical outcomes in LLD. Methods: Ninety older adults (50 LLD and 40 controls (HC)) participated in the study. Blood was collected and exosomes were isolated using size-exclusion chromatography. DNA was extracted and EX-mtDNA levels and deletion were assessed using qPCR. Plasma TNFRI and TNFRII levels were quantified by multiplex immunoassay. Correlation analysis explored relationships between EX-mtDNA, clinical outcomes, and inflammatory markers. Results: Although no differences were observed in EX-mtDNA levels between groups, elevated levels correlated with poorer cognitive performance (r = − 0.328, p = 0.002) and increased TNFRII levels (r = 0.367, p = 0.004). LLD exhibited higher deletion rates (F(83,1) = 4.402, p = 0.039), with a trend remaining after adjusting for covariates (p = 0.084). Deletion correlated with poorer cognitive performance (r = − 0.335, p = 0.002). No other associations were found. Limitation: Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center. Conclusion: Our findings suggest that EX-mtDNA holds promise as an indicator of cognitive outcomes in LLD. Additional research is needed to further comprehend the role of EX-mtDNA levels/integrity in LLD, paving the way for its clinical application in the future.
dc.description.sponsorshipCAMH Discovery Fund Seed Funding Competition
dc.description.versionPeer Reviewed
dc.identifier.citationMendes-Silva, A. P., Nikolova, Y. S., Rajji, T. K., Kennedy, J. L., Diniz, B. S., Gonçalves, V. F., & Vieira, E. L. (2024). Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults. Journal of Affective Disorders, 362, 217–224. https://doi.org/10.1016/j.jad.2024.06.092
dc.identifier.doihttps://doi.org/10.1016/j.jad.2024.06.092
dc.identifier.urihttps://hdl.handle.net/10388/16200
dc.language.isoen
dc.publisherJournal of Affective Disorders
dc.subjectexosomes
dc.subjectmitochondrial DNA
dc.subjectlate-life depression
dc.subjectcognitive function
dc.subjectinflammation
dc.titleExosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults
dc.typeArticle

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