BACKGROUND: No comprehensive meta-analysis has ever been performed to assess the 
value of neurofilament light chain (NfL) as a biomarker in genetic ataxia.
OBJECTIVE: We conducted a meta-analysis to summarize NfL concentration and 
evaluate its utility as a biomarker in genetic ataxia.
METHODS: Studies were included if they reported NfL concentration of genetic 
ataxia. We used log (mean ± SD) NfL to describe mean raw value of NfL. The 
effect size of NfL between genetic ataxia and healthy controls (HC) was 
expressed by mean difference. Correlation between NfL and disease severity was 
calculated.
RESULTS: We identified 11 studies of 624 HC and 1006 patients, here referred to 
as spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia (FRDA), and 
ataxia telangiectasia (A-T). The concentration of blood NfL (bNfL) elevated with 
proximity to expected onset, and progressively increased from asymptomatic to 
preclinical to clinical stage in SCA3. Compared with HC, bNfL levels were 
significantly higher in SCA1, 2, 3, and 7, FRDA, as well as A-T, and the 
difference increased with the advancing disease in SCA3. bNfL levels correlated 
with disease severity in SCA3. There was a significant correlation between bNfL 
and longitudinal progression in SCA3. Additionally, bNfL increased with age in 
HC, yet this is probably masked by higher disease-related effects on bNfL in 
genetic ataxia.
CONCLUSIONS: bNfL can be used as a potential biomarker to predict disease onset, 
severity, and progression of genetic ataxia. Reference-value setting of bNfL 
should be divided according to age. © 2021 International Parkinson and Movement 
Disorder Society.