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

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.