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

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.