Plasma cortisol levels in amyotrophic lateral sclerosis

2013

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

2018

© 2018 Elsevier Inc.

Prognostic Role of CSF β-amyloid 1–42/1–40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis

2021

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1–42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1–40 and Aβ 1–42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a signi…

ALS monocyte-derived microglia reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disea…

2020

AbstractAimsAmyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Neuroinflammation mediated by microglial activation is evident in post-mortem brain tissues, and in brain imaging of patients with ALS. However, the exact role of microglia in ALS remains to be elucidated partly due to the lack of an accurate microglial model system that is able to recapitulate the clinical pathology of ALS. Moreover, direct sampling of microglia from patients with ALS is not feasible, further limiting the study of microglial function in ALS. To address this shortcoming, we describe an approach that generates monocyte-deri…

Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders

2022

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn…

Plasma cortisol level in amyotrophic lateral sclerosis

2015

Background. Amyotrophic Lateral sclerosis (ALS) is associated with a significant distress, being linked to changes in hypothalamic-pituitary-adrenal axis activity. A loss of cortisol circadian rhythmicity in ALS patients was suggested, while more recently an increased plasma cortisol level in the disease has been reported. Objective. To assay the circadian plasma cortisol level in ALS and to study its relationship with the clinical phenotype and the rate of disease progression. Patients and methods. 135 ALS patients (Bulbar, 33; Spinal, 102; M/F = 1.73) and 110 controls (not affected by neurological or psychiatric disorders, free of drugs; M/F = 1.75) were recruited. Disease progression was…

CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis

2017

Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF of ALS patients from a single tertiary Center and investigated their relationship with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%; Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were recruited. Demographic and clinical variables were recorded, and Delta FS was used to rate the disease progression. Controls were divided i…

Expression of vesicle-associated membrane-protein-associated protein B cleavage products in peripheral blood leukocytes and cerebrospinal fluid of pa…

2013

Background and purpose Vesicle-associated membrane-protein-associated protein B (VAPB) is an endoplasmic reticulum (ER) resident protein participating in ER function, vesicle trafficking, calcium homeostasis and lipid transport. Its N-terminal domain, named MSP, is cleaved and secreted, serving as an extracellular ligand. VAPB mutations are linked to autosomal-dominant motor neuron diseases, including amyotrophic lateral sclerosis (ALS) type 8. An altered VAPB function is also suspected in sporadic ALS (SALS). Methods The expression pattern of VAPB cleavage and secreted products in the peripheral blood leukocytes (PBL) and cerebrospinal fluid (CSF) of SALS patients and neurological controls…

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

2020

BACKGROUND AND PURPOSE To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. METHODS We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. R…

ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated…

2022

Abstract Background Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterised by the loss of upper and lower motor neurons. Increasing evidence indicates that neuroinflammation mediated by microglia contributes to ALS pathogenesis. This microglial activation is evident in post-mortem brain tissues and neuroimaging data from patients with ALS. However, the role of microglia in the pathogenesis and progression of amyotrophic lateral sclerosis remains unclear, partly due to the lack of a model system that is able to faithfully recapitulate the clinical pathology of ALS. To address this shortcoming, we describe an approach that generates monocyte-derived mi…

MTHFR C677T allelic variant is not associated to plasma and cerebrospinal fluid homocysteine in amyotrophic lateral sclerosis

2014

Amiotrophic lateral sclerosis (ALS) is a neurological disorder with a multifactorial etiopathogenesis including excitotoxicity, intracellular calcium increase and mitochondrial damage together with oxidative stress and apoptosis. Overall, the relationship between homocysteine (Hcy), motoneuron death and ALS appears to be complex and still under investigation. It has been already shown that Hcy is elevated in plasma and cerebrospinal fluid (CSF) of ALS patients, although mechanisms of hyperhomocysteinemia have not been elucidated yet. MTHFR C677T variant is the most common genetic determinant of increased homocysteinemia, but no studies regarding the effect of this polymorphism in ALS patien…

URIC ACID LEVELS IN SERUM AND CSF OF ALS PATIENTS

2009

Objective: Urate (UA) is a potent antioxidant that effectively scavenges reactive nitrogen and oxygen radicals, and persons with a high plasma UA level may be at lower risk of some neurodegenerative disorders, as Parkinson’s disease (PD). Low plasma UA level has been observed in Alzheimer’s disease (AD) and vascular dementia, but there is no data on correlations to neuropsychological test results in these patient groups. Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron disease, with a highly variable rate of progression and whose diagnosis is chiefly based on clinical and neurophysiological parameters. The etiopathogenesis is unknown, but the oxidative stress seems to play …

Additional file 1 of ALS monocyte-derived microglia-like cells reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of ph…

2022

Additional file 1. Additional tables and figures.

HFE p.H63D polymorphism does not influence ALS phenotype and survival.

2015

It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significa…

TOXICITY OF B-N-OXALYLAMINO-L-ALANINE ANDB-N-METHYLAMINO-L-ALANINE IN NIH3T3 CELLS IS MEDIATED BY INHIBITIONOF THE XC¯ ANTIPORTER

2012

Beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are two non-protein amino acids reported to induce neuronal degeneration. They have been involved in the pathogenesis of rare motor neuron diseases, as neurolathyrism or the ALS-Parkinson-Dementia complex of Guam. The mechanisms by which BOAA and BMAA toxicity is explicated is still unknown, but there is evidence that it might involve the inhibition of Xc¯ antiporter, that is the rate-limiting transporter of the synthesis of intracellular glutathione. In the present study, we investigated the mechanisms of BOAA and BMAA toxicity in the non-neuronal NIH3T3 cells. First, we treated NIH3T3 cells with BOAA or BMAA at di…