Zombosomes are anucleated cell couriers that spread α-synuclein pathology

Astrocytes not only play a central role in orchestrating the brain's microenvironment but also are tightly connected to neurodegenerative processes. Hence, unraveling astrocytes' intercellular pathways can give important insight into disease-spreading mechanisms. Here, we describe a distinct form of actively migrating cellular vehicles, which we have named zombosomes. Zombosomes shed from astrocytes but retain their adhesive and motile properties, even though they lack nuclei. They share protein markers with their parental astrocytes, including highly packed vimentin, and are loaded with intact organelles. Importantly, zombosomes act as disease couriers, transferring α-synuclein aggregates from one cell to another, and have the capacity to infiltrate and induce pathology in cerebral organoids. Human brain sections show scattered vimentin-rich zombosomes with no attachments to nearby astrocytes, which contain deposits of aggregated α-synuclein. Taken together, our findings represent an interaction pathway between distant cells through "live" vehicles that when misused, may cause propagation of Parkinson's disease pathology.