CSF markers in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS, 'Lou Gehrig disease') is the most common, progressive, neurodegenerative, motor neuron disease, causing damage to upper and lower motor neurons, leading to paralysis and death within 3-5 years. Majority of ALS cases are sporadic ALS (SALS) and only 5-10 % of cases are familial ALS (FALS). Pathogenesis of ALS is complicated and still unclear, including genetic, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, neurofilament accumulation, impaired trophic support, altered glial function, viral infection, immune imbalance and impairment of the blood-brain, blood-spinal cord and blood-cerebrospinal fluid barriers (BBB/BSCB/BCSFB). The CSF analysis is still one of the basic laboratory tools and might reflect pathophysiological alterations in the course of the disease and could provide an insight into disease pathomechanisms. The most important aim of its analysis is evaluation of blood-CSF barrier, which is altered in 46 % of ALS patients. The CSF biomarkers may give insight into ALS pathophysiology and may be useful for early, presymptomatic diagnosis, therapeutic monitoring and the development of new therapeutic strategies. This review summarizes the general concepts of biomarkers in CSF of ALS patients and their potential usefulness in further research.

Recent Advances and Applications of Metabolomics to Investigate Neurodegenerative Diseases

“…CSF sample analysis in ALS is particularly important because 46% of ALS patients have blood-CSF barrier alterations (Tarasiuk et al, 2012). Thus, CSF analysis could provide insight into disease pathomechanisms.…”

“…Compared to AD and PD, ALS is less frequent, accounting with an annual incidence rate around 2 per 100,000 individuals (Kiernan et al, 2011). ALS is the most common motor neuron disease affecting upper and lower motor neurons and leading to paralysis and death within 3-5 years (Tarasiuk, Kułakowska, Drozdowski, Kornhuber, & Lewczuk, 2012). Epidemiologically, it is of particular relevance to point out that nearly 20 million people worldwide suffer the devastating effects of these three chronic pathologies (Mayeux, 2003).…”

Cross-Sectional Survey of Relevant Literatures as to the Current Proposed Disease Mechanisms and Treatments of Amyotrophic Lateral Sclerosis (ALS)

“…Degeneration of the blood-CSF barrier is observed in 46% of ALS patients 11 and offers a suggestive area of clinical assessment. Still, markers of blood brain barrier impairment, blood-spinal cord barrier impairment, blood-CSF barrier impairment, neuroaxonal degeneration, oxidative stress, neurotransmission, inflammation, immune activation, and glial activation have not yet yielded clinically relevant information in the diagnosis of ALS.…”

“…Still, markers of blood brain barrier impairment, blood-spinal cord barrier impairment, blood-CSF barrier impairment, neuroaxonal degeneration, oxidative stress, neurotransmission, inflammation, immune activation, and glial activation have not yet yielded clinically relevant information in the diagnosis of ALS. 11,12 While many of these markers are present in cases of ALS, they are not exclusive to this disease and have as yet presented a unique and reproducible clinical profile. However advancements have been made in other neurodegenerative diseases, with reductions in CSF cAMP and cGMP concentrations in Creutzfeldt-Jakob disease but not in ALS.…”

Alteration of Motor Protein Expression Involved in Bidirectional Transport in Peripheral Blood Mononuclear Cells of Patients with Amyotrophic Lateral Sclerosis

“…Despite a high number of studies and numerous hypotheses, the causes and molecular and pathogenic mechanisms of SALS are still unclear [8]. There is no specific marker, and the therapy is largely palliative [4,9,10,11]. …”