Plasma PolyQ-ATXN3 Levels Associate With Cerebellar Degeneration and Behavioral Abnormalities in a New AAV-Based SCA3 Mouse Model

• DOI: 10.3389/fcell.2022.863089
• Publication Date: 2022-03-21T05:53:05Z
• Authors: Karen Jansen-West; Tiffany W. Todd; Lillian M. Daughrity; Mei Yue; Jimei Tong; Yari Carlomagno; Giulia Del Rosso; Aishe Kurti; Caroline Y. Jones; Judith A. Dunmore; Monica Castanedes...; Dennis W. Dickson; Zbigniew K. Wszolek; John D. Fryer; Leonard Petrucelli; Mercedes Prudencio
• Keywords: Cerebellar Degeneration; Machado–Joseph disease; Degeneration (medical)

Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited cerebellar caused by the expansion of polyglutamine (polyQ) repeat in gene encoding ATXN3. The polyQ induces protein inclusion formation neurons patients and results neuronal degeneration cerebellum other brain regions. We used adeno-associated virus (AAV) technology to develop new mouse model SCA3 that recapitulates several features human disease, including locomotor defects, cerebellar-specific loss, polyQ-expanded ATXN3 inclusions, TDP-43 pathology. also found neurofilament light elevated cerebrospinal fluid (CSF) animals, expanded polyQ-ATXN3 can be detected plasma. Interestingly, levels plasma correlated with measures deficits 6-month-old mice, supporting hypothesis this factor could act as biomarker for SCA3.