Levy Lab Investigates the Role of Extracellular Vesicles in Aging and Neurodegeneration

For over ten years, Dr. Efrat Levy and members of her laboratory have been studying vesicular transport as it relates to neurodegenerative disorders such as Alzheimer’s disease. In particular, they have been investigating the role of extracellular vesicles (EVs) and over time they have developed increasingly powerful methods of isolating and analyzing these minute particles. Papers published in 2012 and in 2017 described a novel method to isolate EVs from the interstitial fluid of the brain. The lab has used this method for the analyses of brain EVs during aging, in patients with neurodegenerative diseases such as Alzheimer’s disease, in individuals with Down syndrome, in murine models of spinocerebellar ataxia and chronic cocaine exposure and in subjects carrying the apolipoprotein E4 allele, the greatest genetic risk factor for Alzheimer’s disease.

EVs are heterogeneous and encompass vesicles with different intracellular origins, functions, and molecular markers. Therefore, the Levy lab continuously worked to improve the original protocol to better fractionate known and novel brain EVs. The latest milestone on their journey is a recent publication titled, “Isolation of mitochondria-derived mitovesicles and subpopulations of microvesicles and exosomes from brain tissues,” in the August 2022 issue of Nature Protocols which details a high-resolution fractionation technique that better separates subpopulations of the known extracellular vesicles, the plasma membrane derived microvesicles and the late endosome-derived exosomes. Most importantly, the improved protocol revealed the existence of a different, previously unidentified type of EV that derives from mitochondria and that the authors named mitovesicles. The Nature Protocols article is accompanied by an Aug. 12, 2022 online “Behind the  Paper” feature authored by Dr. Pasquale D’Acunzo.

Dr. Levy’s laboratory is currently studying the pathways involved in mitovesicle exocytosis and the effects of their internalization, investigating the physiological and pathogenic roles of mitovesicles in the brain. The discovery of mitovesicles paves the way to study novel mechanisms that are relevant for neurodegenerative diseases and that likely have a contributive role in the development of dementia. Accordingly, mitovesicle research may suggest in the future novel and unexplored therapeutic directions and be useful to identify new diagnostic/prognostic markers in the blood.