Urine levels of the polyglutamine ataxin-3 protein are elevated in patients with spinocerebellar ataxia type 3

Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients. We analyzed urine samples from 30 SCA3 subjects (including one pre-symptomatic subject), 35 subjects with other forms of ataxia, and 37 healthy controls. To quantify polyQ ATXN3 protein levels, we used our previously developed immunoassay. PolyQ ATXN3 can be detected in the urine of SCA3 patients, but not in urine samples from healthy controls or other forms of ataxia. There was a significant statistical association between polyQ ATXN3 levels in urine samples and those in plasma. Further, the levels of polyQ ATXN3 urine associated with an earlier age of SCA3 disease onset. As clinical trials for SCA3 advance, urine polyQ ATXN3 protein has potential to be a useful, non-invasive and inexpensive biomarker for SCA3. [Display omitted] •PolyQ ATXN3 accumulate in urine samples from SCA3 patients.•Urine may be preferably collected from SCA3 patients over CSF and blood.•Urine polyQ ATXN3 levels associate with an earlier age of SCA3 onset.•Measuring polyQ ATXN3 in urine may be of interest during SCA3 clinical trials.