Association of serum neurofilament light and disease severity in patients with spinocerebellar ataxia type 3
| Autor: | Weihua Liao, Jingyi Tang, Yuting Shi, Peng Huirong, Youming Zhang, Xue-wei Zhang, Qiyong Cai, Chunrong Wang, Puzhi Wang, Thomas Klockgether, Hong Jiang, Jennifer Zhang, Shaohui Liu, Linlin Wan, Tianjiao Li, Yun Peng, Na Wan, Chen Zhao, Yue Xie, Hongyu Yuan, Beisha Tang, Rong Qiu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine blood [Neurofilament Proteins] Severity of Illness Index Gastroenterology blood [Machado-Joseph Disease] physiopathology [Machado-Joseph Disease] 0302 clinical medicine pathology [Gray Matter] Neurofilament Proteins Interquartile range pathology [White Matter] Gray Matter Young adult Ataxin-3 blood [Biomarkers] medicine.diagnostic_test Machado-Joseph Disease Middle Aged Magnetic Resonance Imaging White Matter medicine.anatomical_structure pathology [Machado-Joseph Disease] Spinocerebellar ataxia Female medicine.symptom Adult Heterozygote medicine.medical_specialty Ataxia Asymptomatic diagnostic imaging [White Matter] White matter Young Adult 03 medical and health sciences genetics [Ataxin-3] Internal medicine Severity of illness medicine Humans ddc:610 neurofilament protein L business.industry diagnostic imaging [Gray Matter] ATXN3 protein human Magnetic resonance imaging medicine.disease diagnosis [Machado-Joseph Disease] Repressor Proteins genetics [Repressor Proteins] Cross-Sectional Studies 030104 developmental biology Mutation Neurology (clinical) business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | Neurology 95(22), e2977-e2987 (2020). doi:10.1212/WNL.0000000000010671 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.0000000000010671 |
| Popis: | ObjectiveTo investigate serum neurofilament light protein (sNfL) levels in patients with spinocerebellar ataxia type 3 (SCA3) and to determine whether they are associated with disease severity.MethodsThis cross-sectional study enrolled 185 healthy controls and 235 ATXN3 mutation carriers (17 asymptomatic stage, 20 preclinical stage, and 198 ataxic stage). We measured sNfL levels with the single molecule array (Simoa) platform. Clinical disease severity was assessed using the Scale of Assessment and Rating of Ataxia (SARA) and the Inventory of Nonataxia Signs (INAS). In a subgroup of 50 ataxic stage patients, we further evaluated the gray matter volume and the integrity of white matter fibers by MRI.ResultssNfL concentrations were elevated in asymptomatic, preclinical, and ataxic ATXN3 mutation carriers compared to controls (12.18 [10.20–13.92], 21.84 [18.37–23.45], 36.06 [30.04–45.90], and 8.24 [5.92–10.84] pg/mL, median [interquartile range], respectively, p < 0.001). sNfL correlated with SARA (r = 0.406, 95% confidence interval [CI] 0.284–0.515, p < 0.0001) and INAS (r = 0.375, 95% CI 0.250–0.487, p < 0.0001), and remained significant after adjustment for age and CAG repeats. In addition, we observed negative correlations of the sNfL with gray matter volume in the left precentral gyrus and the left paracentral lobule as well as with the mean diffusivity in widespread white matter tracts.ConclusionOur results demonstrate that sNfL levels are increased in SCA3 and are associated with clinical disease severity, which supports sNfL as a biomarker for disease severity in SCA3.Classification of evidenceThis study provides Class II evidence that in patients with SCA3, sNfL elevations are associated with clinical disease severity. |
| Databáze: | OpenAIRE |
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