Barriers in the Nervous System: Challenges and Opportunities for Novel Biomarkers in Amyotrophic Lateral Sclerosis

• Published in: Cells (Basel, Switzerland) Vol. 14; no. 11; p. 848
• Main Authors: Pisoni, Lorena, Donini, Luisa, Gagni, Paola, Pennuto, Maria, Ratti, Antonia, Verde, Federico, Ticozzi, Nicola, Mandrioli, Jessica, Calvo, Andrea, Basso, Manuela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.06.2025; MDPI
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - metabolism; Amyotrophic Lateral Sclerosis - pathology; Analysis; Animals; Biological markers; Biomarkers; Biomarkers - metabolism; Blood vessels; blood–brain barrier; blood–CSF barrier; blood–spinal cord barrier; Central nervous system; Cerebrospinal fluid; Cytochrome; Disease; Extracellular Vesicles - metabolism; Humans; Microbiota; Nervous system; Nervous system diseases; Neurodegenerative diseases; Neurons; Prognosis; Proteins; Review; Smooth muscle; Spinal cord; Italy; blood–brain barrier; blood–spinal cord barrier; blood–CSF barrier; review
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells14110848

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by wide phenotypic heterogeneity. Despite efforts to carefully define and stratify ALS patients according to their clinical and genetic features, prognosis prediction still remains unreliable. Biomarkers that reflect changes in the central nervous system would be useful, but the physical impossibility of direct sampling and analysis of the nervous system makes them challenging to validate. A highly explored option is the identification of neuronal-specific markers that could be analyzed in peripheral biofluids. This review focuses on the description of the physical and biological barriers to the central nervous system and of the composition of biofluids in which ALS disease biomarkers are actively searched. Finally, we comment on already validated biomarkers, such as the neurofilament light chain, and show the potential of extracellular vesicles (EVs) and cell-free DNA as additional biomarkers for disease prediction.