Blood Neurofilament Light Chain in Genetic Ataxia: A Meta-Analysis

Linliu Peng¹, Shang Wang¹, Zhao Chen¹²³⁴, Yun Peng¹, Chunrong Wang⁵, Zhe Long⁶, Huirong Peng¹, Yuting Shi¹, Xuan Hou¹, Lijing Lei¹, Linlin Wan¹, Mingjie Liu¹, Guangdong Zou¹, Lu Shen¹²³⁴, Kun Xia⁷⁸, Rong Qiu⁹, Beisha Tang¹²³⁴, Tetsuo Ashizawa¹⁰¹¹, Thomas Klockgether¹²¹³, Hong Jiang¹²³⁴¹⁴

Affiliations

¹Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
²National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China.
⁴Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China.
⁵Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
⁶Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
⁷Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
⁸Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China.
⁹School of Computer Science and Engineering, Central South University, Changsha, China.
¹⁰Neuroscience Research Program, Houston Methodist Research Institute, Houston, Texas, USA.
¹¹Stanley H. Appel Department of Neurology, Weill Cornell Medicine at Houston Methodist Hospital, Houston, Texas, USA.
¹²Department of Neurology, University of Bonn, Bonn, Germany.
¹³German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹⁴School of Basic Medical Science, Central South University, Changsha, China.

PMID: 34519102
DOI: 10.1002/mds.28783

Abstract

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.

Keywords: biomarker; disease severity and progression; genetic ataxia; meta-analysis; neurofilament light chain.