Carboxy‐terminal truncations of mouse α‐synuclein alter aggregation and prion‐like seeding

α‐synuclein (αsyn) forms pathologic inclusions in several neurodegenerative diseases termed synucleinopathies. The inclusions are comprised of αsyn fibrils harboring prion‐like properties. Prion‐like activity of αsyn has been studied by intracerebral injection of fibrils into mice, where the presence of a species barrier requires the use of mouse αsyn. Post‐translational modifications to αsyn such as carboxy (C)‐terminal truncation occur in synucleinopathies, and their implications for prion‐like aggregation and seeding are under investigation. Herein, C‐truncated forms of αsyn found in human disease are recapitulated in mouse αsyn to study their seeding activity in vitro, in HEK293T cells, in neuronal–glial culture, and in nontransgenic mice. The results show that C‐truncation of mouse αsyn accelerates aggregation of αsyn but alters prion‐like seeding of inclusion formation.