Identification of Gal(β1-3)GalNAc bearing glycoproteins in cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients

2000 ◽  
Vol 7 (6) ◽  
pp. 679-683 ◽  
Author(s):  
I. Niebroj-Dobosz ◽  
A. Mickielewicz ◽  
K. Rowiñska-Marciñska ◽  
H. Kwieciñski
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Als Patients ◽  
Lateral Sclerosis

scholarly journals Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1210
Author(s):  
Júlia Costa ◽  
Marta Gromicho ◽  
Ana Pronto-Laborinho ◽  
Conceição Almeida ◽  
Ricardo A. Gomes ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Motor Neurons ◽  
Neurological Diseases ◽  
Disease Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Progression Rate ◽  
Therapeutic Trials ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

scholarly journals Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion

2016 ◽  
Vol 6 (1) ◽  
pp. 142-149 ◽  
Author(s):  
Anna Junttila ◽  
Mari Kuvaja ◽  
Päivi Hartikainen ◽  
Maritta Siloaho ◽  
Seppo Helisalmi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Lobar Degeneration ◽  
Rapid Progression ◽  
Carrier Status ◽  
C9orf72 Expansion ◽  
Main Protein ◽  
Als Patients ◽  
T Tau ◽  
Lateral Sclerosis

Background: TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables. Methods: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, Aβ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. Results: There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). Conclusion: CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.

Anti-neural antibodies in serum and cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients

2009 ◽  
Vol 100 (4) ◽  
pp. 238-243 ◽  
Author(s):  
I. Niebroj-Dobosz ◽  
Z. Jamrozik ◽  
P. Janik ◽  
I. Hausmanowa-Petrusewicz ◽  
H. Kwiecinski
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Als Patients ◽  
Lateral Sclerosis

scholarly journals Human Spinal Motor Neurons Are Particularly Vulnerable to Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients

2020 ◽  
Vol 21 (10) ◽  
pp. 3564 ◽  
Author(s):  
Stefan Bräuer ◽  
René Günther ◽  
Jared Sterneckert ◽  
Hannes Glaß ◽  
Andreas Hermann
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Harmful Effect ◽  
Model Systems ◽  
Early Event ◽  
Human Patient ◽  
Sporadic Als ◽  
Golgi Fragmentation ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common and devastating motor neuron (MN) disease. Its pathophysiological cascade is still enigmatic. More than 90% of ALS patients suffer from sporadic ALS, which makes it specifically demanding to generate appropriate model systems. One interesting aspect considering the seeding, spreading and further disease development of ALS is the cerebrospinal fluid (CSF). We therefore asked whether CSF from sporadic ALS patients is capable of causing disease typical changes in human patient-derived spinal MN cultures and thus could represent a novel model system for sporadic ALS. By using induced pluripotent stem cell (iPSC)-derived MNs from healthy controls and monogenetic forms of ALS we could demonstrate a harmful effect of ALS-CSF on healthy donor-derived human MNs. Golgi fragmentation—a typical finding in lower organism models and human postmortem tissue—was induced solely by addition of ALS-CSF, but not control-CSF. No other neurodegenerative hallmarks—including pathological protein aggregation—were found, underpinning Golgi fragmentation as early event in the neurodegenerative cascade. Of note, these changes occurred predominantly in MNs, the cell type primarily affected in ALS. We thus present a novel way to model early features of sporadic ALS.

Neurofilament Subunit L Levels in the Cerebrospinal Fluid and Serum of Patients with Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 18 (2-3) ◽  
pp. 165-172 ◽  
Author(s):  
Zhong-Ying Gong ◽  
Gao-Peng Lv ◽  
Li-Na Gao ◽  
Yi Lu ◽  
Jie Guo ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Rating Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Progression Rate ◽  
Serum Samples ◽  
High Level ◽  
Als Patients ◽  
Lateral Sclerosis

Background: There are no reliable biomarkers that could evaluate the disease burden in amyotrophic lateral sclerosis (ALS). Objectives: The aim of our study is to evaluate the changes in cerebrospinal fluid (CSF) and serum neurofilament subunit L (NF-L) in patients with ALS and to analyze the correlations between the levels of NF-L and clinical parameters. Method: CSF and serum samples were obtained from 80 ALS patients and 40 controls. The levels of NF-L in CSF and serum were assessed, and disease progression parameters including duration, revised ALS Functional Rating Scale (ALSFRS-r) score, disease progression rate (DPR), upper motor neuron (UMN) score, and survival were analyzed by registered neurologists. All samples were measured using a commercial enzyme-linked immunosorbent assay. Statistical analyses were performed using Prism software. Results: Compared to the controls, the ALS patients displayed significantly increased levels of NF-L; these values were negatively correlated with the ALSFRS-r score and positively correlated with the decrease in ALSFRS-r score, DPR, and UMN score. There was no correlation between levels of NF-L and duration. In addition, the cumulative survival rate in ALS patients with a low level of NF-L was higher than in patients with a high level of NF-L. Conclusions: NF-L levels increased in CSF and serum of patients with ALS. NF-L may thus be a neurodegenerative biomarker for predicting ALS severity and progression, and the survival of patients with this disease.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 17 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Si Chen ◽  
Qiao Liao ◽  
Ke Lu ◽  
Jinxia Zhou ◽  
Cao Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rat Model ◽  
Microglial Activation ◽  
Transgenic Rat ◽  
Intragastric Administration ◽  
Behavioral Deficits ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

scholarly journals Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takamasa Nukui ◽  
Atsushi Matsui ◽  
Hideki Niimi ◽  
Tomoyuki Sugimoto ◽  
Tomohiro Hayashi ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Serum Creatinine ◽  
Disease Severity ◽  
Assay System ◽  
Atp Levels ◽  
Sum Score ◽  
Highly Sensitive ◽  
Severe Group ◽  
Lateral Sclerosis

Abstract Background Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08). Conclusions Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

Plasma Creatinine Level Does Not Predict Respiratory Function in Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-5
Author(s):  
João Morgadinho ◽  
Ana Catarina Pronto-Laborinho ◽  
Vasco A. Conceição ◽  
Marta Gromicho ◽  
Susana Pinto ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Creatinine Level ◽  
Cox Regression ◽  
Functional Decline ◽  
Plasma Creatinine ◽  
Plasma Creatinine Level ◽  
Decline Rate ◽  
Respiratory Outcome ◽  
Als Patients ◽  
Lateral Sclerosis

In amyotrophic lateral sclerosis (ALS) lower plasma creatinine level has been associated with shorter survival and faster functional decline. It has not been clear if creatinine is associated with respiratory outcome. We analyzed retrospectively a population of unselected ALS patients. Multiple-regression and Cox-regression analyses were performed. We included 233 patients, mean age 62.8, mean disease duration of 18.6 months. At baseline, creatinine was significantly associated with ALSFRS-R, but not with its decline rate. No predictive value was disclosed for FVC, or their decline rate, or with survival. We did not confirm that creatinine is a marker of respiratory outcome.

Coping strategies among amyotrophic lateral sclerosis (ALS) patients: an integrative review

2021 ◽  
Author(s):  
Georgiana Soares Leandro ◽  
Mário Emílio Teixeira Dourado Júnior ◽  
Glauciane Costa Santana ◽  
Luan Samy Xavier Dantas
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Coping Strategies ◽  
Integrative Review ◽  
Als Patients ◽  
Lateral Sclerosis

scholarly journals Sterol auto-oxidation adversely affects human motor neuron viability and is a neuropathological feature of amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James C. Dodge ◽  
Jinlong Yu ◽  
S. Pablo Sardi ◽  
Lamya S. Shihabuddin
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Cholesterol Homeostasis ◽  
Cholesterol Oxidation ◽  
Therapeutic Approaches ◽  
Cellular Survival ◽  
Sporadic Als ◽  
Human Motor ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractAberrant cholesterol homeostasis is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease that is due to motor neuron (MN) death. Cellular toxicity from excess cholesterol is averted when it is enzymatically oxidized to oxysterols and bile acids (BAs) to promote its removal. In contrast, the auto oxidation of excess cholesterol is often detrimental to cellular survival. Although oxidized metabolites of cholesterol are altered in the blood and CSF of ALS patients, it is unknown if increased cholesterol oxidation occurs in the SC during ALS, and if exposure to oxidized cholesterol metabolites affects human MN viability. Here, we show that in the SOD1G93A mouse model of ALS that several oxysterols, BAs and auto oxidized sterols are increased in the lumbar SC, plasma, and feces during disease. Similar changes in cholesterol oxidation were found in the cervical SC of sporadic ALS patients. Notably, auto-oxidized sterols, but not oxysterols and BAs, were toxic to iPSC derived human MNs. Thus, increased cholesterol oxidation is a manifestation of ALS and non-regulated sterol oxidation likely contributes to MN death. Developing therapeutic approaches to restore cholesterol homeostasis in the SC may lead to a treatment for ALS.

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