scholarly journals TDP-43 and HERV-K Envelope-Specific Immunogenic Epitopes Are Recognized in ALS Patients

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2301
Author(s):  
Elena Rita Simula ◽  
Giannina Arru ◽  
Ignazio Roberto Zarbo ◽  
Paolo Solla ◽  
Leonardo A. Sechi
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Humoral Response ◽  
Dna Binding Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Als Patients ◽  
Circulating Levels ◽  
Lateral Sclerosis

The human endogenous retrovirus-K (HERV-K) and TAR DNA-binding protein 43 (TDP-43) have been associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the humoral response against HERV-K envelope surface (env-su) glycoprotein antigens and TDP-43 in the plasma of ALS patients and healthy controls (HCs). The measured levels of Abs against the different epitopes’ fragments were significantly elevated in ALS patients, both in long-survivor (LS) and newly diagnosed (ND) patients, compared to HCs. We observed a positive correlation between HERV-K and TDP-43 antibodies (Abs) levels, which seemed to strengthen with disease progression, that was not found in HCs. The TDP-43 and HERV-K epitopes identified in this study are highly immunogenic and recognized by the humoral response of ALS patients. Increased circulating levels of Abs directed against specific HERV-K- and TDP-43-derived epitopes could serve as possible biomarkers.

scholarly journals Changes in the concentrations of trimethylamine N-oxide (TMAO) and its precursors in patients with amyotrophic lateral sclerosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lu Chen ◽  
Yong Chen ◽  
Mingming Zhao ◽  
Lemin Zheng ◽  
Dongsheng Fan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Gut Microbiota ◽  
Metabolic Pathway ◽  
Plasma Concentrations ◽  
Disease Onset ◽  
Healthy Controls ◽  
Age And Gender ◽  
And Gender ◽  
Als Patients ◽  
Lateral Sclerosis

Abstract To compare the plasma concentrations of trimethylamine N-oxide (TMAO) and its precursors in amyotrophic lateral sclerosis (ALS) patients, their spouses and healthy controls and to find associations between gut microbiota metabolites and ALS. ALS patients were recruited at Peking University Third Hospital from January 2015 to December 2018. Information was collected from their spouses at the same time. Age and gender matched healthy controls were recruited from individuals who visited the physical examination center for health checkups. Blood samples were collected after at least 4 h of fasting. Concentrations of the metabolites were quantified using stable isotope dilution liquid chromatography–tandem mass spectrometry. Group differences were analyzed using parametric and nonparametric tests, as appropriate. In this study, 160 patients with ALS were recruited. In these patients, 63 were compared with their spouses, 148 were compared with age and gender matched controls, and 60 were compared with both their spouses and heathy controls in the same time. The carnitine concentration was significantly higher in patients than in their spouses, while there were no significant differences in the concentrations of other metabolites. The carnitine and betaine concentrations were higher, while the choline, TMAO and butyrobetaine concentrations were lower in ALS than in healthy controls. The concentrations of the metabolites in the spouses were more similar to the ALS patients rather than to the healthy controls. In the ALS group, the plasma concentrations of carnitine, betaine, choline and TMAO were inversely related to the severity of upper motor neuron impairment. The TMAO metabolic pathway of the gut microbiota is disturbed in both ALS patients and their spouses, which might suggest that the changes in the gut microbiota occurred before disease onset. The negative correlations between the involvement of UMNs and the concentrations of the metabolites might suggest that the inhibition of this metabolic pathway might lead to a better prognosis in ALS patients.

scholarly journals Poor Bone Quality in Patients With Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Jordi Caplliure-Llopis ◽  
Dolores Escrivá ◽  
María Benlloch ◽  
José Enrique de la Rubia Ortí ◽  
José María Estrela ◽  
...  
Keyword(s):  
Vitamin D ◽  
Amyotrophic Lateral Sclerosis ◽  
Bone Health ◽  
Clinical Status ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Bone Parameters ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Tsh Levels

Objective: Musculoskeletal functional deterioration in Amyotrophic lateral sclerosis (ALS) is associated with an increase in bone fractures. The purpose of this study was to evaluate the influence of sex, ALS type, on bone quality in patients with ALS compared to healthy controls. The impact on bone health of the clinical status and some metabolic parameters was also analyzed in ALS patients.Methods: A series of 33 voluntary patients with ALS, and 66 healthy individuals matched in sex and age underwent assessment of bone mass quality using quantitative ultrasound (QUS) of the calcaneus. Ultrasonic broadband attenuation (BUA), the speed of sound (SOS), stiffness index and T-score were measured. Bone mineral density (BMD) was estimated using standard equations. Apart from fat and muscle mass percentage determinations, clinical baseline measures in ALS patients included ALSFRS-R score, Barthel index for activities of daily living, pulmonary function measured using FVC, and muscular strength assessed by a modified MRC grading scale. Laboratory tests included serum calcium, 25-HO-cholecalciferol (Vitamin D), alkaline phosphatase (ALP), T4 and TSH.Results: All bone parameters evaluated were statistically significant lower in ALS patients than in healthy controls. ALS females showed significantly lower bone parameters than healthy females. According to the estimated BMD, there were 25 ALS patients (75.8%) and 36 (54.5%) healthy individuals showing an osteoporotic profile (BMD <0.700 g/cm2). Only 16.7% of the ALS females had T-scores indicative of healthy bones. There was no correlation between any of the clinical parameters analyzed and the bone QUS measurements. Vitamin D and TSH levels positively correlated with all the bone parameters.Conclusions: This study confirms that ALS patients, particularly females, exhibited deteriorated bone health as compared to healthy individuals. These structural bone changes were independent of ALS subtype and clinical status. Bone health in ALS patients seems to be related to certain metabolic parameters such as Vitamin D and TSH levels.

scholarly journals Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

2017 ◽  
Vol 75 (5) ◽  
pp. 272-276 ◽  
Author(s):  
Marcelo Chaves ◽  
Mariela Bettini ◽  
Maria Cecilia Fernandez ◽  
Maria Jose Garcia Basalo ◽  
Juan Ignacio Rojas ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Cognitive Profile ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Preliminary Study ◽  
Als Patients ◽  
Lateral Sclerosis

ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.

scholarly journals The Incidence of Amyotrophic Lateral Sclerosis in Ohio 2016–2018: The Ohio Population-Based ALS Registry

2021 ◽  
pp. 1-10
Author(s):  
Angeline S. Andrew ◽  
Erik P. Pioro ◽  
Meifang Li ◽  
Xun Shi ◽  
Jiang Gui ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rural Areas ◽  
Clinical Information ◽  
Population Based ◽  
Incidence Rates ◽  
The State ◽  
Newly Diagnosed ◽  
Disease Etiology ◽  
Als Patients ◽  
Lateral Sclerosis

<b><i>Introduction:</i></b> Amyotrophic lateral sclerosis (ALS) is a fatal, neuromuscular disease with no cure. ALS incidence rates have not been assessed specifically in Ohio, yet the state contains both metropolitan and rural areas with a variety of environmental factors that could contribute to disease etiology. We report the incidence of ALS in Ohio residents diagnosed from October 2016 through September 2018. <b><i>Methods:</i></b> We engaged practitioners from 9 Ohio sites to identify newly diagnosed ALS patients and to complete case report forms with demographic and clinical information. ALS was diagnosed according to the Awaji criteria and classified as either definite, probable, or possible. We developed a method to estimate missing cases using a Poisson regression model to impute cases in counties with evidence of undercounting. <b><i>Results:</i></b> We identified 333 newly diagnosed ALS patients residing in Ohio during the 2-year index period and found incidence rates varied in the 88 state counties. After incorporating the estimated 27% of missing cases, the corrected crude annual incidence was 1.96/100,000 person-years, and the age- and gender-standardized incidence was 1.71/100,000 person-years (standardized to the 2010 US census). <b><i>Discussion/Conclusion:</i></b> The estimated Ohio incidence of ALS is overall similar to that reported in other states in the USA. This study reveals a geospatial variation in incidence within the state, and areas with higher rates warrant future investigation.

scholarly journals Quantitative susceptibility-weighted imaging in amyotrophic lateral sclerosis with 3.0 T magnetic resonance imaging

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199222
Author(s):  
Meng-Yu Liu ◽  
Zhi-Ye Chen ◽  
Jin-Feng Li ◽  
Hua-Feng Xiao ◽  
Lin Ma
Keyword(s):  
Magnetic Resonance Imaging ◽  
Amyotrophic Lateral Sclerosis ◽  
Phase Shift ◽  
Susceptibility Weighted Imaging ◽  
Precentral Gyrus ◽  
Healthy Controls ◽  
Resonance Imaging ◽  
3.0 T ◽  
Als Patients ◽  
Lateral Sclerosis

Objective To evaluate alterations in phase-shift values in the gray matter of patients with amyotrophic lateral sclerosis (ALS) using susceptibility-weighted imaging (SWI). Methods Twenty patients with definite or probable ALS and 19 age- and sex-matched healthy controls were enrolled. SWI was performed using a 3.0 T magnetic resonance imaging scanner. Phase-shift values were measured in corrected phase images using regions of interest, which were placed on the bilateral precentral gyrus, frontal cortex, caudate nucleus, globus pallidus, and putamen. Results Phase-shift values of the precentral gyrus were significantly lower in ALS patients (−0.176 ± 0.050) than in the control group (−0.119 ± 0.016) on SWI. The average phase-shift values of the frontal cortex, caudate nucleus, globus pallidus, and putamen in ALS patients (−0.089 ± 0.023, −0.065 ± 0.016, −0.336 ± 0.191, and −0.227 ± 0.101, respectively) were not significantly different from those in the healthy controls (−0.885 ± 0.015, −0.079 ± 0.018, −0.329 ± 0.136, and −0.229 ± 0.083, respectively). Conclusions Compared with healthy controls, ALS patients had a lower phase-shift value in the precentral gyrus, which may be related to abnormal iron overload. Thus, SWI is a potential method for identifying ALS patients.

scholarly journals Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

2021 ◽  
Vol 15 ◽  
Author(s):  
Haining Li ◽  
Qiuli Zhang ◽  
Qianqian Duan ◽  
Jiaoting Jin ◽  
Fangfang Hu ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Correlation Analysis ◽  
Disease Severity ◽  
Structural Changes ◽  
Diffusion Tensor ◽  
Healthy Controls ◽  
Significant Difference ◽  
Als Patients ◽  
And Diffusion ◽  
Lateral Sclerosis

IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

Macroscopic Localized Subicular Thinning as a Potential Indicator of Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 79 (3-4) ◽  
pp. 200-205 ◽  
Author(s):  
Hiroki Yamada ◽  
Takahiro Takeda ◽  
Toshiki Uchihara ◽  
Shizuko Sato ◽  
Susumu Kirimura ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nucleus Accumbens ◽  
Dna Binding ◽  
Alzheimer Disease ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Potential Indicator ◽  
Transentorhinal Cortex ◽  
Als Patients ◽  
Lateral Sclerosis

Subicular degeneration occurs in amyotrophic lateral sclerosis (ALS) patients. However, it was unknown whether microscopic subicular degeneration could be observed as macroscopic changes and whether these changes were associated with the transactive-response DNA binding protein 43 kDa (TDP-43) pathology. Topographic differences between subicular degeneration caused by ALS and Alzheimer disease (AD) had also not been characterized. Here we investigated the subiculum and related areas in autopsied brains from 3 ALS and 3 AD patients. Macroscopic subicular thinning and corresponding astrocytosis were pronounced in ALS compared to AD. This thinning was frequently accompanied by TDP-43 pathology in the transentorhinal cortex and nucleus accumbens. The preferential susceptibility of the perforant pathway to TDP-43 deposition may be an underlying cause of subicular thinning in ALS.

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