Exploring CSF biomarkers in amyotrophic lateral sclerosis: Highlighting the significance of TDP-43
Journal
Journal of the Neurological Sciences
Journal Volume
472
Start Page
123479
ISSN
0022-510X
Date Issued
2025-05-15
Author(s)
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the existence of the TAR DNA-binding protein 43 (TDP-43) aggregates in motor neurons. This study investigated specific cerebrospinal fluid (CSF) biomarkers, including TDP-43, as diagnostic or prognostic biomarkers for ALS. The study included a hospital-based cohort of sporadic ALS patients (N = 30) and age-matched controls (N = 19). Using immunomagnetic reduction technology, CSF levels of TDP-43, neurofilament light chain (NfL), phosphorylated tau 181 (p-tau181), and total tau (t-tau) were assessed. Plasma levels of TDP-43 were also measured. The association of the different biomarkers with disease severity was investigated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and compound muscle action potential (CMAP) amplitudes. The rate of disease progression was evaluated by measuring decline in ALSFRS-R over time. ALS patients had higher CSF NfL and lower ratio of p-tau181/t-tau than control subjects. No significant difference between groups was observed in CSF TDP-43. In ALS patients, CSF levels of any biomarker, including TDP-43, were not associated with ALSFRS-R scores, FVC, or mean CMAP amplitudes. However, CSF TDP-43 positively correlated with the rate of decline in ALSFRS-R (p = 0.042). ALS patients with high CSF TDP-43 levels (>5 pg/mL) showed larger decline in ALSFRS-R (14.0 ± 11.90 vs. 8.8 ± 5.48 per year; p = 0.045) than those with lower TDP-43. Plasma TDP-43 levels did not correlate with CSF TDP-43 or any clinical parameter. CSF TDP-43 is associated with the rate of disease progression and may be a prognostic biomarker in patients with sporadic ALS.
Subjects
Amyotrophic lateral sclerosis
Biomarker
Cerebrospinal fluid
Neurofilament
TDP-43
SDGs
Type
journal article