Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons, causing relentless paralysis. There is a need for ALS biomarkers in order to facilitate early and differential diagnosis and prediction of disease course. The most promising ALS biomarkers are neurofilaments (phosphorylated heavy chain [pNFH] and light chain [NFL]), for which increasing evidence probably warrants their introduction in the clinical scenario in the near future. Their levels are raised in the CSF of ALS patients as a consequence of release from degenerating motor neuron axons, therefore enabling differentiation from most other conditions. Neurofilaments also have prognostic value, predicting survival and correlating with disease progression rate. Thanks to technological advances, neurofilaments can now be measured also in the blood, providing information which is similar to that given by their CSF counterparts. As neurofilament levels are stable over time and blood sampling makes longitudinal measurements easy, they are particularly promising as pharmacodynamic biomarkers for trials of experimental therapeutics. Another class of ALS biomarkers is that of neuroinflammatory molecules, among which the chitinases, and particularly chitotriosidase (Chit1), have been most studied in the last years. Though significantly raised in the CSF in ALS, the diagnostic performance of Chit1 is actually lower than that of neurofilaments; its potential usefulness is rather due to the fact that it presumably reflects microglial inflammation occurring in the non-cell-autonomous neurodegenerative process, which, together with the longitudinal stability of CSF levels, would enable its use as a pharmacodynamic biomarker in future trials targeting neuroinflammation.

Amyotrophic Lateral Sclerosis: Neurochemical Biomarkers / F. Verde, N. Ticozzi - In: Acquired Neuromuscular Disorders : Pathogenesis, Diagnosis and Treatment: Second Edition / [a cura di] C. Angelini. - [s.l] : Springer, 2022. - ISBN 9783031067303. - pp. 295-310 [10.1007/978-3-031-06731-0_16]

Amyotrophic Lateral Sclerosis: Neurochemical Biomarkers

F. Verde;N. Ticozzi
2022

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons, causing relentless paralysis. There is a need for ALS biomarkers in order to facilitate early and differential diagnosis and prediction of disease course. The most promising ALS biomarkers are neurofilaments (phosphorylated heavy chain [pNFH] and light chain [NFL]), for which increasing evidence probably warrants their introduction in the clinical scenario in the near future. Their levels are raised in the CSF of ALS patients as a consequence of release from degenerating motor neuron axons, therefore enabling differentiation from most other conditions. Neurofilaments also have prognostic value, predicting survival and correlating with disease progression rate. Thanks to technological advances, neurofilaments can now be measured also in the blood, providing information which is similar to that given by their CSF counterparts. As neurofilament levels are stable over time and blood sampling makes longitudinal measurements easy, they are particularly promising as pharmacodynamic biomarkers for trials of experimental therapeutics. Another class of ALS biomarkers is that of neuroinflammatory molecules, among which the chitinases, and particularly chitotriosidase (Chit1), have been most studied in the last years. Though significantly raised in the CSF in ALS, the diagnostic performance of Chit1 is actually lower than that of neurofilaments; its potential usefulness is rather due to the fact that it presumably reflects microglial inflammation occurring in the non-cell-autonomous neurodegenerative process, which, together with the longitudinal stability of CSF levels, would enable its use as a pharmacodynamic biomarker in future trials targeting neuroinflammation.
Amyotrophic lateral sclerosis (ALS); Biomarkers; Cerebrospinal fluid; CHI3L1 (YKL-40); CHI3L2; Chitinases; Chitotriosidase (Chit1); Motor neuron disease (MND); Neurofilaments
Settore MED/26 - Neurologia
2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1032029
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