The Levy Laboratory Describes a Method to Isolate a Novel Type of Extracellular Vesicle from the Brain

Pasquale D'Acunzo

A new paper published in Nature Protocols by Pasquale D’Acunzo, Yohan Kim, Jonathan M. Ungania, Rocío Pérez-González, Chris N. Goulbourne, and Efrat Levy, all current or former members of the Center for Dementia Research (CDR), describes in great detail a method to isolate, fractionate, and analyze subpopulations of extracellular vesicles from the extracellular space of the brain. Extracellular vesicles are very small membrane-bound, heterogeneous, spherical structures containing proteins, RNA, and DNA that shuttle from cells into the extracellular milieu and from one cell to the other in order to eliminate waste from cells and to exchange information and material between cells.

Typical hallmarks of neurodegenerative diseases such as Alzheimer’s disease include the spreading of pathology from a single focal site to the rest of the brain and impairment in the processing of material, which eventually accumulates both inside and outside the cells, becoming toxic to neurons. Extracellular vesicles have roles in both the maintenance of homeostasis in the normal brain and in pathological processes in neurodegenerative disorders. Therefore, they have attracted scientific interest, growing exponentially in the last decade.

Pathogenic hotspots in the brain during aging, in neurodegenerative, neurodevelopmental, and psychiatric disorders include mitochondrial failure and endosomal-lysosomal system dysfunction, which likely play causative roles in neuron degeneration. Separation and identification of different subtypes of extracellular vesicles enable the discovery of roles that the different types of vesicles play in these conditions and initiate the development of novel therapeutic and diagnostic tools, capitalizing on the biology of brain extracellular vesicles.

The Levy laboratory is an international leader in the study of extracellular vesicles in the brain and was the first in 2012 to report a method to isolate these vesicles from the brain, paving the way for a new line of research in the field. Through the intervening decade, the laboratory has continuously worked to improve this method in order to identify the heterogeneity of extracellular vesicles in the brain. The culmination of these efforts led to the development of a high-resolution fractionation technique that separates eight extracellular vesicle subpopulations, including a previously unidentified subtype of extracellular vesicles of mitochondrial origin that the authors named mitovesicles. The final, improved method is described in the recently published paper in Nature Protocols in great detail.

Reference: D’Acunzo P, Kim Y, Ungania JM, Pérez-González R, Goulbourne CN, Levy E. Isolation of mitochondria-derived mitovesicles and subpopulations of microvesicles and exosomes from brain tissues. Nat Protoc. 2022 Aug 12. doi: 10.1038/s41596-022-00719-1. PMID: 35962195.