BDNF and Pro-BDNF in Amyotrophic Lateral Sclerosis: A New Perspective for Biomarkers of Neurodegeneration

Le résumé fourni par la source

Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of upper or lower motor neurons, leading to muscle wasting and paralysis, resulting in respiratory failure and death. The precise ALS aetiology is poorly understood, mainly due to clinical and genetic heterogeneity. Thus, the identification of reliable biomarkers of disease could be helpful in clinical practice. In this study, we investigated whether the levels of brain-derived neurotrophic factor (BDNF) and its precursor Pro-BDNF in serum and cerebrospinal fluid (CSF) may reflect the pathological changes related to ALS. We found higher BDNF and lower Pro-BDNF levels in ALS sera compared to healthy controls. BDNF/Pro-BDNF ratio turned out to be accurate in distinguishing ALS patients from controls. Then, the correlations of these markers with several ALS clinical variables were evaluated. This analysis revealed three statistically significant associations: (1) Patients carrying the C9orf72 expansion significantly differed from non-carrier patients and showed serum BDNF levels comparable to control subjects; (2) BDNF levels in CSF were significantly higher in ALS patients with faster disease progression; (3) lower serum levels of Pro-BDNF were associated with a shorter survival. Therefore, we suggest that BDNF and Pro-BDNF, alone or in combination, might be used as ALS prognostic biomarkers.

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