SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study
European journal of neurology(2024)
Abstract
Background: SerpinA1, a serine protease inhibitor, is involved in the modulation of microglial-mediated inflammation in neurodegenerative diseases. We explored SerpinA1 levels in cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients to understand its potential role in the pathogenesis of the disease. Methods: SerpinA1, neurofilament light (NfL) and heavy (NfH) chain, and chitinase-3-like protein-1 (CHI3L1) were determined in CSF and serum of ALS patients (n = 110) and healthy controls (n = 10) (automated next-generation ELISA), and correlated with clinical parameters, after identifying three classes of progressors (fast, intermediate, slow). Biomarker levels were analyzed for diagnostic power and association with progression and survival. Results: SerpinA1(serum) was significantly decreased in ALS (median: 1032 mu g/mL) compared with controls (1343 mu g/mL) (p = 0.02). SerpinA1(CSF) was elevated only in fast progressors (8.6 mu g/mL) compared with slow (4.43 mu g/mL, p = 0.01) and intermediate (4.42 mu g/mL, p = 0.03) progressors. Moreover, SerpinA1(CSF) correlated with neurofilament and CHI3L1 levels in CSF. Contrarily to SerpinA1(CSF), neurofilament and CHI3L1 concentrations in CSF correlated with measures of disease progression in ALS, while SerpinA1(serum) mildly related with time to generalization (rho = 0.20, p = 0.04). In multivariate analysis, the ratio between serum and CSF SerpinA1 (SerpinA1 ratio) and NfH(CSF) were independently associated with survival. Conclusions: Higher SerpinA1(CSF) levels are found in fast progressors, suggesting SerpinA1 is a component of the neuroinflammatory mechanisms acting upon fast-progressing forms of ALS. Both neurofilaments or CHI3L1(CSF) levels outperformed SerpinA1 at predicting disease progression rate in our cohort, and so the prognostic value of SerpinA1 alone as a measure remains inconclusive.
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Key words
ALS,biomarker,serpinA1
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