%0 Journal Article
%T Exosome-associated mitochondrial DNA in late-life depression: Implications for cognitive decline in older adults.
%A Mendes-Silva AP
%A Nikolova YS
%A Rajji TK
%A Kennedy JL
%A Diniz BS
%A Gonçalves VF
%A Vieira EL
%J J Affect Disord
%V 362
%N 0
%D 2024 Jun 28
%M 38945405
%F 6.533
%R 10.1016/j.jad.2024.06.092
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>Cross-sectional study with a small number of participants from a specialized geriatric psychiatry treatment center.<BR><B>CONCLUSIONS: </B>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.