CNS Mitochondria-Derived Vesicle in Blood: Potential Biomarkers for Brain Mitochondria Dysfunction

Authors:

Qi Liu, Wentao Chen, Yahong Wu, Zhen Guo, Jun Chen, Chen Tian, Pan Wang, Shaopeng Zeng, Bin Xu, Jing Duan, Shilong Han, Xiao Xiong, Jing Zhang

Keywords:

Mitochondrial dysfunction; mitochondria; neurodegenerative disease; MDV; mitochondria-derived vesicles; biomarker

Abstract:

Objective: Mitochondrial dysfunction is a hallmark of neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s (PD). Our goal was to develop practical, noninvasive methods to assess mitochondrial status through the detection of mitochondria-derived vesicles (MDVs).

Methods: We explored blood-borne MDVs, a recently identified class of extracellular vesicles, as potential biomarkers for CNS mitochondrial status.

Results: The study identified MDVs from neurons, astrocytes, and oligodendrocytes specifically in human plasma. A novel nanoflow cytometry was developed to evaluate the level of neuron-, astrocyte-, and oligodendrocyte-derived MDVs in plasma in AD and PD patients. Importantly, analyses of discovery and validation cohorts revealed significantly lower brain cell-specific MDVs in AD and PD patients compared to healthy controls.

Interpretation: This study suggests that blood MDVs could serve as noninvasive biomarkers for mitochondrial dysfunction in AD, PD, and beyond, potentially aiding in monitoring mitochondrial-focused therapies for neurological disorders.

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