scholarly journals The Clinical Significance of Cerebrospinal Fluid Reticulon 4 (RTN4) Levels in the Differential Diagnosis of Neurodegenerative Diseases

2021 ◽  
Vol 10 (22) ◽  
pp. 5281
Author(s):  
Agnieszka Kulczyńska-Przybik ◽  
Maciej Dulewicz ◽  
Agnieszka Słowik ◽  
Renata Borawska ◽  
Alina Kułakowska ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Neurodegenerative Diseases ◽  
Clinical Utility ◽  
Newly Diagnosed ◽  
Protein Levels ◽  
Significant Difference ◽  
Causes Of Mortality ◽  
Diagnostic Approaches ◽  
Immunological Assays

Neurodegenerative diseases (NDs) belong to the top global causes of mortality. Diagnostic approaches to improve early diagnosis and differentiation of these diseases are constantly being sought. Therefore, we aimed to assess the cerebrospinal fluid (CSF) concentrations of Reticulon 4 (RTN4) in patients with neurodegenerative diseases and evaluate the potential clinical usefulness of this protein. RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. According to our best knowledge, this is the first investigation providing the data concerning the dynamic of CSF RTN4 protein levels in patients with different NDs. Methods: Overall, 77 newly diagnosed patients with neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), as well as 21 controls, were enrolled in the study. The CSF concentrations of tested proteins were assessed using immunological assays. Results: We revealed significantly higher CSF RTN4A levels in patients with AD, PD, and MS in comparison to the controls. Moreover, the comparative analysis of RTN4 concentration between different neurodegenerative diseases revealed the highest concentration of RTN4A in AD patients and a statistically significant difference between AD vs. PD, and AD vs. MS groups. The increased CSF level of the protein correlated with Tau, and pTau181 proteins in AD as well as in PD patients. Conclusions: Our study presents a previously not identified clinical utility of RTN4 in the differential diagnosis of neurodegenerative diseases.

scholarly journals Total alpha-synuclein assay in cerebrospinal fluid is of interest in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies from the prodromal stage

2020 ◽  
Author(s):  
Olivier BOUSIGES ◽  
Nathalie Philippi ◽  
Thomas Lavaux ◽  
Armand Perret-Liaudet ◽  
Ingolf Lachmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prodromal Stage ◽  
Significant Difference

Abstract Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage.Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d) and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42 and Aβ40) were also measured.Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Furthermore, alpha-synuclein levels were elevated not only in AD patients with a typical “Alzheimer” profile (i.e. 2 or 3 pathological biomarkers) but also in AD patients with an atypical “Alzheimer” profile (i.e. one or no pathological biomarkers).Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. Moreover, alpha-synuclein assay appears to be of particular interest in the differential diagnosis of AD in cases where the Alzheimer biomarkers do not have a typical profile of the disease, i.e. when there is only one or no pathological biomarkers.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identifier: NCT01876459)

scholarly journals The Diagnostic and Differential Diagnosis Utility of Cerebrospinal Fluidα-Synuclein Levels in Parkinson’s Disease: A Meta-Analysis

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bo Zhou ◽  
Min Wen ◽  
Wen-Feng Yu ◽  
Chun-Lin Zhang ◽  
Ling Jiao
Keyword(s):  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Dementia With Lewy Bodies ◽  
Meta Analysis ◽  
Lewy Bodies ◽  
Diagnostic Biomarker ◽  
Inclusion Criteria ◽  
Human Cerebrospinal Fluid ◽  
Significant Difference ◽  
Mean Concentration

Several recent studies showed thatα-syn might be a potential diagnostic biomarker for PD in human cerebrospinal fluid (CSF), but the results were inconsistent. The purpose of this meta-analysis was to investigate the diagnostic and differential diagnosis efficacy of CSFα-syn in PD. Studies which measured CSFα-syn orα-syn oligomers in patients with PD and met the inclusion criteria were included in the analysis. Results of the meta-analysis indicated that mean concentration of CSFα-syn was significantly lower in PD compared to controls and significantly higher in PD compared to multiple system atrophy (MSA). No significant difference in mean concentration of CSFα-syn was found between PD and dementia with Lewy bodies (DLB). Mean concentration of CSFα-syn was slightly decreased in PD compared to progressive supranuclear palsy (PSP). Mean concentration of CSFα-syn oligomers was significantly higher in PD than control. These results support the findings that CSFα-syn may be a potential diagnostic and differential diagnosis biomarker in PD compared to control and MSA but not DLB. Furthermore,α-syn oligomer may represent a better biomarker for diagnosis of PD.

Event-related Potentials Improve the Efficiency of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Alzheimer’s Disease

2018 ◽  
Vol 15 (13) ◽  
pp. 1244-1260 ◽  
Author(s):  
Mirjana Babić Leko ◽  
Magdalena Krbot Skorić ◽  
Nataša Klepac ◽  
Fran Borovečki ◽  
Lea Langer Horvat ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cerebrospinal Fluid ◽  
Differential Diagnosis ◽  
Tau Protein ◽  
Strong Correlation ◽  
Event Related Potentials ◽  
P300 Latency ◽  
Protein Biomarkers ◽  
Related Potentials ◽  
T Tau

Introduction: The pathological process of Alzheimer's disease (AD) in the brain likely begins 20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively by electroencephalography have shown diagnostic potential in AD. Aims: The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including amyloid β peptide (β1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI) and AD patients. Subjects: The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16 patients with other primary causes of dementia. Results: ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation between ERP and neuropsychological testing and showed that P300 latency and RT are shortened in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients with high risk for development of AD in our cohort. MCI patients with pathological levels of Aβ1-42 had prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential of P300 latency in differentiating AD and FTD patients. Conclusion: Our data provide possible solutions for improvement of differential diagnosis of AD, and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in clinical practice.

In silico Defining the Repeat-containing Proteins in the Acinetobacter baumannii Proteome, a Great Reservoir of Templates for Synthetic Biology

2019 ◽  
Vol 13 (2) ◽  
pp. 149-158
Author(s):  
Mohammad Reza Rahbar ◽  
Mahboubeh Zarei ◽  
Navid Nezafat ◽  
Manica Negahdaripour ◽  
Younes Ghasemi
Keyword(s):  
Acinetobacter Baumannii ◽  
Drug Targets ◽  
Closely Related Species ◽  
Great Ability ◽  
Repeat Proteins ◽  
Significant Difference ◽  
Biological Determinants ◽  
Tandem Repeat Proteins ◽  
Diagnostic Approaches ◽  
Novel Therapeutic

Background: Acinetobacter baumannii is an important nosocomial pathogen with great ability to resist antibiotics. Tandem repeat proteins, abundant in prokaryotic proteomes, attract attention due to their role in virulence and various biological processes. Defining repeat- containing proteins may pave the way to find novel therapeutic targets as well as vaccine candidate and give pieces of evidence of mechanisms of evolution and adaptation of organisms to various environmental conditions. Objective: In the present study, we employed bioinformatics tools to define repeatcontaining proteins within A. baumannii proteome for emphasizing the existence of natural sources for synthesizing novel therapeutic and diagnosis material. Results: We defined various kinds of repeat modules in a number of proteins and compared the abundance of these proteins in some closely related species. No significant difference was observed in the count of repeat-containing proteins in different species. But the existence of some important virulence factors is mentionable in our screening. Conclusion: Repeat containing proteins are important biological determinants of A. baumannii and are well worth researching for finding drug targets and vaccine candidates. These proteins can be served as a template for designing and synthesizing peptides for therapeutic and diagnostic approaches.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

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