Systematic assessment of plasma biomarkers in spinocerebellar ataxia

脊髓小脑共济失调 共济失调 内科学 萎缩 医学 蒙特利尔认知评估 胃肠病学 病理 心理学 肿瘤科 认知障碍 疾病 精神科
作者
Xue‐Ning Shen,Kaimin Wu,Yu‐Yuan Huang,Xiao‐Qi Yu,Shu‐Yi Huang,Yaru Zhang,Shufen Chen,Hui-Fu Wang,Wei Zhang,Wei Cheng,Mei Cui,Qiang Dong,Jin‐Tai Yu
出处
期刊:Neurobiology of Disease [Elsevier]
卷期号:181: 106112-106112 被引量:4
标识
DOI:10.1016/j.nbd.2023.106112
摘要

Plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), phosphorylated-tau (p-tau), and β-amyloid (Aβ) have emerged as promising markers in several neurodegenerative disorders, but whether they can be used as biomarkers in spinocerebellar ataxias (SCA) is yet to be determined. This study aimed to identify sensitive plasma markers for SCA and investigate their effectiveness in tracking ataxia severity, cognition, non-motor symptoms, and brain atrophy.This observational study recruited consecutive participants from Huashan Hospital and the CABLE study from November 2019. Patients with SCA were genetically diagnosed, grouped according to the ataxia severity, and compared with healthy older individuals and patients with multiple system atrophy type C (MSA-C). Plasma NfL, GFAP, p-tau, and Aβ levels were measured by Simoa in all participants. Analysis of covariance, Spearman correlation, and multivariable regression were used to explore candidate markers in SCA.A total of 190 participants (60 SCA, 56 MSA-C, and 74 healthy controls) were enrolled. Plasma NfL level increased early in the pre-ataxic stage of SCA (32.23 ± 3.07 vs. 11.41 ± 6.62 pg/mL in controls), was positively associated with the ataxia severity (r = 0.45, P = 0.005) and CAG repeat length (r = 0.51, P = 0.001), varied among the different SCA subtypes (39.57 ± 13.50 pg/mL in SCA3, which was higher than 28.17 ± 8.02 pg/mL in SCA2, 17.08 ± 6.78 pg/mL in SCA8, and 24.44 ± 18.97 pg/mL in rare SCAs; P < 0.05), and was associated with brainstem atrophy. NfL alone (area under the curve [AUC] 0.867) or combined with p-tau181 and Aβ (AUC 0.929), showed excellent performance in discriminating SCA patients from controls. Plasma GFAP distinguished SCA from MSA-C with moderate accuracy (AUC > 0.700) and correlated with cognitive performance and cortical atrophy. Changes in levels of p-tau181 and Aβ were observed in SCA patients compared to controls. They were both correlated with cognition, while Aβ was also associated with non-motor symptoms, such as anxiety and depression.Plasma NfL may serve as a sensitive biomarker for SCA, and its level is elevated in the pre-ataxic stage. The different performance of NfL and GFAP indicates differences in the underlying neuropathology of SCA and MSA-C. Moreover, amyloid markers may be useful for detecting memory dysfunction and other non-motor symptoms in SCA.
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