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Blood–brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia

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Abstract

Objective

We aim to investigate blood–brain barrier (BBB) dysfunction and myelin basic protein (MBP) in amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD) and further determine the effect of these factors on the survival of ALS.

Methods

This was a retrospective study of 113 ALS patients, 12 ALS-FTD patients, and 40 disease controls hospitalized between September 2013 and October 2020. CSF parameters including total protein (TP), albumin (Alb), immunoglobulin-G (IgG), and MBP were collected and compared between groups. The CSF-TP, CSF-Alb, CSF-IgG, and CSF/serum quotients of Alb and IgG (QAlb, QIgG) were used to reflect the BBB status. Patients were followed up until December 2020. Cox regression and Kaplan–Meier method were used for survival analysis.

Results

The CSF-TP, CSF-Alb, and CSF-IgG concentrations were significantly higher in patients than controls (p < 0.01). Increased CSF-TP and CSF-IgG was found in 45 (39.8%) and 27 (23.9%) ALS patients, while in 7 (58.3%) and 5 (41.7%) ALS-FTD patients. The level of CSF-Alb, CSF-IgG, and CSF-MBP were significantly higher in patients with ALS-FTD than ALS. MBP showed a moderate accuracy in the distinction between ALS-FTD and ALS (AUC = 0.715 ± 0.101). No difference in MBP was found between patients and controls. Kaplan–Meier analysis indicated that a higher CSF-TP, CSF-IgG, QIgG, or QAlb was significantly associated with shorter survival. Cox regression model showed that CSF-TP, CSF-IgG, and QIgG were independent predictors of survival.

Conclusion

Our findings suggested that BBB dysfunction was more prominent in ALS-FTD than ALS and associated with a worse prognosis. Further studies are needed to determine the role of CSF-MBP as a biomarker in ALS.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Acknowledgements

We thank all the patients for their participation in our study, and also thank all the related researchers involved in this study for their help and valuable suggestions.

Funding

This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences (Grant number: XDB39040100), Chinese Academy of Medical Science Neuroscience Center Fund “Molecular diagnosis and pathogenesis of ALS” (Grant number: 2014xh0601_A322102), and “Molecular diagnosis and neural network of ALS” (Grant number: 20141001_A322104).

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Authors and Affiliations

  1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Bei**g, 100730, China

    **-Yue Li, Zheng-Yi Cai, **ao-Han Sun, Dong-chao Shen, Xun-Zhe Yang, Ming-Sheng Liu & Li-Ying Cui

  2. Neuroscience Center, Chinese Academy of Medical Sciences, Bei**g, 100730, China

    Li-Ying Cui

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Contributions

JL: acquisition of data, statistical analysis, and manuscript writing. ZC: data collection. XS: data collection. DS: statistical analysis. XY: data review. ML: manuscript editing. LC: study concept and design, manuscript editing, and critical revision.

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Correspondence to Li-Ying Cui.

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The research was approved by the Ethics Committee of Peking Union Medical College Hospital and informed consent was obtained from all patients.

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Li, JY., Cai, ZY., Sun, XH. et al. Blood–brain barrier dysfunction and myelin basic protein in survival of amyotrophic lateral sclerosis with or without frontotemporal dementia. Neurol Sci 43, 3201–3210 (2022). https://doi.org/10.1007/s10072-021-05731-z

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