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Purpose Experts emphasize that incidence and mortality of colorectal cancer (CRC) is increasing. That is why, its early detection is of utmost importance. Patients with cancer diagnosed in earlier stages have better prognosis and chance for faster implementation of treatment. Consequently, it is vital to search for new parameters that could be useful in its diagnosis. Methods Therefore, we evaluated the usefulness of CXCL5, CXCL14 and CXCL16 in serum of 115 subjects (75 CRC patients and 40 healthy volunteers). Concentrations of all parameters were measured using Luminex. CRP levels were determined by immunoturbidimetry, while levels of classical tumor markers were measured using CMIA. Results Concentrations of CXCL5 were statistically higher in CRC group when compared to healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of CXCL5 and CXCL14 were higher than those of CA 19 − 9. Conclusions Obtained results suggest the usefulness of CXCL5 and CXCL16 in the determination of distant metastases and differentiation between TNM stages, as well as usefulness of CXCL14 and CRP combination in CRC detection. However, further studies concerning their role in CRC progression are crucial to confirm and explain their diagnostic utility and clinical application as biomarkers.

Alzheimer disease (AD) is a chronic and heterogeneous neurodegenerative disorder characterized by complex pathological processes involving neuroinflammation, neurodegeneration, and synaptic dysfunction. Understanding the exact neurobiological mechanisms underlying AD pathology may help to provide a biomarker for early diagnosis or at least for assessment of vulnerability to dementia development. Neural plasticity is defined as a capability of the brain to respond to alterations including aging, injury, or learning, with a crucial role of synaptic elements. Long-term potentiation (LTP) and long-term depression (LTD) are important in regulating synaptic connections between neural cells in functional plasticity. Synaptic loss and impairment of the brain's plasticity in AD leads to cognitive impairment, and one of important roles of synaptic biomarkers is monitoring synaptic dysfunction, response to treatment, and predicting future development of AD. Synaptic biomarkers are undoubtedly very promising in developing novel approach to AD treatment and control, especially in the era of aging of societies, which is one of the most common risk factor of AD. Implementing a widespread measurement of synaptic biomarkers of AD will probably be crucial in early diagnosis of AD, early therapeutic intervention, monitoring progression of the disease, or response to treatment. One of the most important challenges is finding a biomarker whose blood concentration correlates with its level in the central nervous system (CNS). This review aims to present the current status of biomarkers of activity-dependent plasticity and persistent enhancement of synaptic transmission in Alzheimer disease.

The course of COVID-19 in people with multiple sclerosis (PwMS) has been described, while the serological status after SARS-CoV-2 infection or vaccination, especially in patients treated with disease-modifying therapies (DMT), is still under investigation. This is a significant clinical problem, as certain DMTs may predispose to a severe course of viral infections.We analyzed the presence of antibodies against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 in relapsing-remitting PwMS treated with DMT, especially dimethyl fumarate, interferon beta, and glatiramer acetate, in a single multiple sclerosis (MS) centre in north-eastern Poland (the Department of Neurology, Medical University of Bialystok).The presence of antibodies against S and N proteins in PwMS was assessed twice: on visit one (between May and June 2020) (n = 186) and on visit two (between May and June 2021) (n = 88). Samples were taken from 68 individuals on both visits. Demographic and clinical data was collected: duration of MS, Expanded Disability Status Scale Score (EDSS), type of DMT, history of COVID-19 (positive PCR or antigen test in the past), vaccination status, and the type of vaccine.It was shown that on visit one: 3.7% (n = 7) PwMS were positive for IgA against S protein (IgA-S), 3.2% (n = 6) for IgG against S (IgG-S) protein, and none of those examined was positive for IgG against N protein (IgG-N). On visit two, the most common detected antibodies were IgG-S (71.3%; n = 62), then IgA-S (65.1%; n = 55), and the least common was IgG-N (18.2%; n = 16). On visit two: 20.45% of PwMS had a history of a positive SARS-CoV-2 PCR or antigen test during the last year. By the time of visit two, 42.05% (n = 37) of patients who participated in visit two had been full-course vaccinated against COVID-19. It was demonstrated that vaccination against SARS-CoV-2 significantly induces the production of IgG-S and IgA-S (p0.0001), while no difference between vaccinated and unvaccinated patients was shown in the detection of IgG-N. There was no correlation between COVID-19 infection and antibodies against proteins S and N in the study group. Moreover, the presented study did not show any relationship between the ability to produce antibodies against the S protein with any of the used DMTs.According to our study, PwMS treated with dimethyl fumarate, interferon beta, or glatiramer acetate can efficiently produce antibodies against SARS-CoV-2 both after infection and after vaccination.

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, molecular functions, and dynamics of the change concentrations of selected proteins reflecting synaptic and axonal pathology in dementia stages. Neurogranin (Ng), neuronal pentraxin receptor (NPTXR), and Visinin-like protein 1 (VILIP1) concentrations were measured in the cerebrospinal fluid (CSF) of MCI, AD, and non-demented controls (CTRL) using quantitative immunological methods. Gene ontology (GO) enrichment analysis was used for the functional analysis of tested proteins. The CSF Aβ42/Ng ratio was significantly different between all the compared groups. The CSF NPTXR/Ng ratio was significantly different between MCI compared to CTRL and AD compared to CTRL. The GO enrichment analysis revealed that two terms (the Biological Process (BP) and Cellular Component (CC) levels) are significantly enriched for NPTXR and Ng but not for VILIP1. Both Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers for the early diagnosis of the disease. Moreover, both proteins are biochemically associated with classical biomarkers and VILIP-1. Mapping shared molecular and biological functions for the tested proteins by GO enrichment analysis may be beneficial in screening and setting new research targets.

Background/aim The current study aimed to evaluate the clinical utility of the levels of the C-X-C-motif chemokine receptor-2 (CXCR-2) serum receptor in comparison to the carcinoembryonic antigen (CEA) tumor marker and - the C-reactive protein (CRP) inflammatory marker in the diagnosis and prognosis of colorectal cancer (CRC). Materials and methods Our study comprised 59 patients with CRC and 46 healthy subjects. Serum concentrations of the analyzed proteins were measured using enzyme-linked immunosorbent assay, chemiluminescent microparticle immunoassay and immunoturbidimetric methods. Results Serum levels of CXCR-2 were lower, while those of CEA and CRP were significantly higher in CRC patients in comparison to the control group. The diagnostic sensitivity of CXCR-2 was higher than that of CEA, and increased when CXCR-2 analysis was combined with CEA or CRP. Conclusion According to our knowledge, this is the first study concerning the significance of CXCR2 as a CRC biomarker. Measurement of the serum levels of CXCR-2 may improve the diagnosis efficiency of CRC patients, especially in combination with the tumor marker CEA.

Background: Given the significant role of neurodegeneration in the progression of multiple sclerosis (MS) and insufficient therapies, there is an urgent need to better understand this pathology and to find new biomarkers that could provide important insight into the biological mechanisms of the disease. Thus, the present study aimed to compare different neurodegeneration and axonal dysfunction biomarkers in MS and verify their potential clinical usefulness. Methods: A total of 59 patients, who underwent CSF analysis during their diagnostics, were enrolled in the study. Quantitative analysis of neurodegeneration biomarkers was performed through immunological tests. Oligoclonal bands were detected by isoelectric focusing on agarose gel, whereas the concentrations of immunoglobulins and albumin were measured using nephelometry. Results: Our studies showed that NfL, RTN4, and tau protein enabled the differentiation of MS patients from the control group. Additionally, the baseline CSF NfL levels positively correlated with the tau and MRI results, whereas the RTN4 concentrations were associated with the immunoglobulin quotients. The AUC for NfL was the highest among the tested proteins, although the DeLong test of the ROC curves showed no significant difference between the AUCs for NfL and RTN4. Conclusion: The CSF NfL, RTN-4, and tau levels at the time of diagnosis could be potential diagnostic markers of multiple sclerosis, although NfL seems to have the best clinical value.

Every year, almost 2 million people develop colorectal cancer (CRC), which makes it the fourth most common malignancy worldwide. It is also estimated that approximately 48% of CRC patients will die from the disease. Thus, noninvasive and accurate methods for early detection and prevention of CRC are sorely needed. It is suggested that C-X-C motif ligand 1 (CXCL1) and C-X-C motif ligand 8 (CXCL8) as well as their cognate receptors can mediate tumor growth, proliferation, survival, neoangiogenesis and metastasis of malignant cells, including CRC. However, little is known about the clinical significance of these proteins as potential biomarkers for CRC. Therefore, in our review, we performed a comprehensive literature search using the PubMed database to identify original articles that investigated whether CXCL1 and CXCL8 and their receptors play a role in CRC pathogenesis. In summary, our review highlighted the potential significance of CXCL1/CXCR2 and CXCL8/CXCR1,-2 in the diagnosis and progression of CRC as well as indicated their potential therapeutic significance. However, given the non-specific nature of analyzed chemokines and a small number of studies concerning the assessment of blood concentration of these proteins in CRC patients, investigations need to be continued in the future before selected chemokines could be established as biomarkers for CRC.

Colorectal cancer (CRC) is one of the most frequently diagnosed neoplasms. Despite the advances in diagnostic tools and treatments, the number of CRC cases is increasing. Therefore, it is vital to search for new parameters that could be useful in its diagnosis. Thus, we wanted to assess the usefulness of selected CC chemokines (CCL2, CCL4, and CCL15) in CRC. The study included 115 subjects (75 CRC patients and 40 healthy volunteers). The serum concentrations of all parameters were measured using a multiplexing method (Luminex). The CRP levels were determined by immunoturbidimetry, and the classical tumor markers (CEA and CA 19-9) were measured using CMIA (chemiluminescent microparticle immunoassay). The concentrations of all parameters were higher in the CRC group when compared to the healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of all estimated CC chemokines were higher than those of CA 19-9. Interestingly, the obtained results also suggest CCL2’s significance in the determination of local metastases and CCL4’s significance in the determination of distant metastases. However, further studies concerning the role of selected CC chemokines in the course of colorectal cancer are necessary to confirm and to fully clarify their diagnostic utility and their clinical application as markers of CRC development.

Background Tick-Borne Encephalitis (TBE) is a viral infection of the Central Nervous System (CNS) caused by Tick-Borne Encephalitis Virus (TBEV). It might take several clinical courses such as: meningitis, meningoencephalitis or meningoencephalomyelitis. The aim this study was to compare the YKL-40 concentration in cerebrospinal fluid (CSF) of patients with different clinical presentations of TBE and patients with excluded meningitis (control group). Methods The concentration of YKL-40 in CSF was determined using Fujirebio tests (Ghent, Belgium) in 32 patients with TBE: group I—patients with meningoencephalitis (n = 16); group II—patients with meningitis (n = 16). The control group (CG) consisted of 17 patients in whom inflammatory process in central nervous system was excluded. Results The concentration of YKL-40 was significantly higher in encephalitis group than in CG after 7 days from the last dose of treatment. The concentration in patients with neuroinflammation had significantly different concentration of YKL-40 compared to patients with no neuroinflammation control groups. ROC curve analysis indicates that: CSF YKL-40 concentration at cut off 783.87 differentiated TBE patients from CG with 100% specificity and 70% sensitivity and CSF YKL-40 concentration at cut off 980.11 differentiated meningitis from meningoencephalitis with 87.5% specificity and 62.5% sensitivity. Conclusions YKL-40 takes part in TBE pathogenesis, its concentration is the highest at the early stage of Central Nervous System involvement and decreases in the convalescent period. As YKL-40 is significantly higher in meningitis than in meningoencephalitis, it might be used as biomarker in differentiation of these clinical forms of TBE.

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.

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer’s disease. Methods: Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology. Results: The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients. Conclusions: The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD.

Alzheimer’s disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer’s Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.

Alzheimer’s disease is a progressive and deadly neurodegenerative disorder, and one of the most common causes of dementia in the world. Current, insufficiently sensitive and specific methods of early diagnosis and monitoring of this disease prompt a search for new tools. Numerous literature data indicate that the pathogenesis of Alzheimer’s disease (AD) is not limited to the neuronal compartment, but involves various immunological mechanisms. Neuroinflammation has been recognized as a very important process in AD pathology. It seems to play pleiotropic roles, both neuroprotective as well as neurodegenerative, in the development of cognitive impairment depending on the stage of the disease. Mounting evidence demonstrates that inflammatory proteins could be considered biomarkers of disease progression. Therefore, the present review summarizes the role of some inflammatory molecules and their potential utility in the detection and monitoring of dementia severity. The paper also provides a valuable insight into new mechanisms leading to the development of dementia, which might be useful in discovering possible anti-inflammatory treatment.

SARS-CoV-2/Coronavirus 2019 (COVID-19) is responsible for the pandemic, which started in December 2019. In addition to the typical respiratory symptoms, this virus also causes other severe complications, including neurological ones. In diagnostics, serological and polymerase chain reaction tests are useful not only in detecting past infections but can also predict the response to vaccination. It is now believed that an immune mechanism rather than direct viral neuroinvasion is responsible for neurological symptoms. For this reason, it is important to assess the presence of antibodies not only in the serum but also in the cerebrospinal fluid (CSF), especially in the case of neuro-COVID. A particular group of patients are people with multiple sclerosis (MS) whose disease-modifying drugs weaken the immune system and lead to an unpredictable serological response to SARS-CoV-2 infection. Based on available data, the article summarizes the current serological information concerning COVID-19 in CSF in patients with severe neurological complications and in those with MS.

Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy.