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Background and Objectives  Few biochemical markers have been identified in spinocerebellar ataxia type 2 (SCA2). This study aimed to determine the levels of neurofilament light (NfL) in patients with SCA2 and to identify whether they are associated with disease severity.    Methods  Participants were recruited from 1 medical center in China, and individuals with SCA2 were genetically diagnosed. NfL levels were assessed with the single molecule array method. Disease severity was evaluated with the Scale for the Assessment and Rating of Ataxia (SARA), the International Cooperative Ataxia Rating Scale (ICARS), and the Inventory of Non-Ataxia Symptoms (INAS). Cerebellum and brainstem volumes were calculated from neuroimaging measurements. We used the Pearson correlation and partial correlation for correlation analyses.    Results  Forty-nine patients with manifest SCA2, 10 preclinical individuals with SCA2, and 92 controls were enrolled. A high consistency was identified between serum and CSF NfL ( r  = 0.868,  p  &lt; 0.0001). In individuals with SCA2, levels of serum NfL were associated with disease severity (SARA:  r  = 0.425,  p  = 0.003; ICARS:  r  = 0.383,  p  = 0.009; INAS:,  r  = 0.390,  p  = 0.007; cerebellum volume:  r  = −0.393,  p  = 0.024) after adjustment for age. NfL levels were higher close to the expected age at onset in preclinical individuals with SCA2 ( R   2   = 0.43,  p  = 0.04).    Discussion  Levels of serum NfL were correlated with disease intensity in individuals with SCA2 and were higher close to the estimated age at onset in preclinical SCA2. Therefore, NfL is a potential serum biomarker of disease severity in SCA2.    Classification of Evidence  This study provides Class II evidence that elevated NfL levels are associated with disease severity in individuals with SCA2.

Association of the Level of Neurofilament Light With Disease Severity in Patients With Spinocerebellar Ataxia Type 2