1. Biomarkers in cerebrospinal fluid for amyotrophic lateral sclerosis phenotypes.
- Author
-
Zhou J, Zeng Q, Liao Q, Niu Q, Gu W, Su D, Li S, Xiao B, and Bi F
- Subjects
- Humans, Proteomics, HLA-DR alpha-Chains, Biomarkers cerebrospinal fluid, Phenotype, Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis cerebrospinal fluid, Neurodegenerative Diseases
- Abstract
Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons. The motor phenotypes of ALS are highly clinically heterogeneous, and the underlying mechanisms are poorly understood., Methods: A comparative proteomic analysis was performed in the cerebrospinal fluid (CSF) of bulbar-onset (BO) and spinal-onset (SO) ALS patients and controls (n = 14). Five biomarker candidates were selected from a differentially regulated protein pool, and further validation was performed in a larger independent cohort (n = 92) using enzyme-linked immunosorbent assay (ELISA)., Results: A total of 1732 CSF proteins were identified, and 78 differentially expressed proteins were found among BO-ALS patients, SO-ALS patients, and controls. Five promising biomarker candidates were selected for further validation, and lipopolysaccharide-binding protein (LBP) and HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA) were validated. CSF LBP levels were increased in ALS patients compared with controls and higher in BO-ALS versus SO-ALS. The increased CSF LBP levels were correlated with the revised ALS Functional Scale (ALSFRS-R) score. CSF HLA-DRA levels were specifically elevated in BO-ALS patients, and there was no significant difference between SO-ALS patients and controls. Increased HLA-DRA expression was correlated with decreased survival., Interpretation: Our data shows that elevated CSF LBP is a good biomarker for ALS and correlates with clinical severity, and increased HLA-DRA is a specific biomarker for BO-ALS and may predict short survival. It also suggests that the microglial pathway and HLA-II-related adaptive immunity may be differentially involved in ALS phenotypes and may be new therapeutic targets for ALS., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2023
- Full Text
- View/download PDF