Mov Disord: Xiangya Hospital: Neurofilament light chain protein can effectively predict ataxia

Hereditary ataxia is a group of clinically and genetically heterogeneous neurodegenerative diseases characterized by cerebellar ataxia caused by genetic mutations
.

It can be inherited in an autosomal dominant, autosomal recessive, X-linked or mitochondrial manner

The most common subtypes of autosomal dominant ataxia are spinocerebellar ataxia types 1, 2, 3, 6 and 7 (SCA 1, 2, 3, 6 and 7), which are repeated by CAG in the causative gene Amplification (CAGexp) caused
.

Friedreich ataxia ataxia (FRDA) and ataxia capillary vascular ectasia (AT) is the most common autosomal recessive ataxia, respectively, by GAA FXN gene duplication extension (GAAexp) and mutated ATM gene causes
.

Blood vessel

Currently, there is no effective treatment for hereditary ataxia to prevent the disease or prevent its development
.

The clinical need for reliable biomarkers for genetic ataxia has not been met

prevention

Currently, neurofilament light chain (NfL) has become one of the promising candidate biomarkers for diagnosis , progression, prognosis, and evaluation of treatment response to neurological diseases (such as Alzheimer's disease and Huntington's disease)
.

Neurofilament light chain (NfL) has become one of the promising candidate biomarkers for diagnosis , progression, prognosis, and evaluation of treatment response to neurological diseases (such as Alzheimer's disease and Huntington's disease)
.

diagnosis

NfL is a neuron-specific cytoskeletal protein, especially expressed in large-caliber myelinated axons
.

It can be actively (for example, through exosomes) or passively released from neurons, secondary to axonal injury and loss of neuronal membrane integrity, enter the brain interstitium, and freely exchange with cerebrospinal fluid (CSF)

In addition, the NfL flowing to the peripheral circulation is mediated by the arterial basement membrane to drain around the blood vessels, then drain into the neck or lumbar lymph nodes, and finally enter the blood
.

Ideally, it is a sensitive marker of nerve axis damage and can be detected in CSF and peripheral blood

However, a comprehensive meta-analysis has not been conducted to evaluate the potential role of NfL as a biomarker in predicting the occurrence of disease or symptoms, measuring disease severity, tracking disease progression, and monitoring treatment response to genetic ataxia
.

Therefore, Linliu Peng and others of Xiangya Hospital conducted a meta-analysis and summarized the current scientific literature on cNfL and bNfL, including plasma NfL (pNfL) or serum NfL (sNfL) in hereditary ataxia
.

When using NfL levels as a biomarker for hereditary ataxia, this meta-analysis can provide clinical application value

A meta-analysis was performed to summarize the current scientific literature on cNfL and bNfL, including plasma NfL (pNfL) or serum NfL (sNfL) in hereditary ataxia

They found 11 studies involving 624 HC and 1006 patients, referring to spinocerebellar ataxia (SCA1, 2, 3, 6, and 7), Friedreich ataxia ataxia (FRDA), and ataxia Far Qu (AT)
.

The concentration of NfL in the blood (bNfL) increases as the expected onset time approaches, and gradually increases from asymptomatic to preclinical stage in SCA3

In SCA3, there is a significant correlation between bNfL and longitudinal progression
.

In addition, in HC, bNfL increases with age, but this may be masked by the higher impact of disease-related bNfL in hereditary ataxia
.

The significance of this meta-analysis is the discovery: bNfL can be used as a potential biomarker to predict the incidence, severity and progression of hereditary ataxia
.

The reference value setting of bNfL should be divided according to age

bNfL can be used as a potential biomarker to predict the incidence, severity and progression of hereditary ataxia

Original source:
Peng L, Wang S, Chen Z, et al.
Blood Neurofilament Light Chain in Genetic Ataxia: A Meta-Analysis.
  Mov Disord.
Published online September 14, 2021:mds.
28783.
doi:10.
1002/mds.
28783

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