No abstract

Background: Growing body of evidence suggests that the pathogenesis of Alzheimer’s disease (AD), a progressing neurodegenerative condition, is not limited to the neuronal compartment, but also involves various immunological mechanisms. Insoluble Aβ aggregates in the brain can induce the activation of microglia, resulting in the synthesis of proinflammatory mediators, which further can stimulate astrocytic expression of YKL-40. Therefore, the aim of the current review is to present up-to-date data about the role of YKL-40 as a biomarker of AD as well as the possibility of therapeutic strategies targeting neuroinflammation.Objective/Methods: We searched PubMed articles for the terms “YKL-40”, “neurodegeneration”, “neuroinflammation” and “Alzheimer’s disease”, and included papers focusing on this review’s scope.Results:Recent studies indicate that CSF concentrations of YKL-40 were significantly higher in AD patients than in cognitively normal individuals and correlated with dementia biomarkers, such as tau proteins and amyloid beta. Determination of YKL-40 CSF concentration may be also helpful in differentiation between types of dementia and in the distinction of patients in the stable phase of MCI from those who progressed to dementia. Moreover, significantly increased levels of YKL-40 mRNA were found in AD brains in comparison with non-demented controls. Additionally, it was suggested that anti-inflammatory treatment might relief the symptoms of AD and slow its progression.Conclusion: Based on the recent knowledge, YKL-40 might be useful as a possible biomarker in the diagnosis and prognosis of AD. Modulation of risk factors and targeting of immune mechanisms, including systemic inflammation could lead to future preventive or therapeutic strategies for AD.

Calcium ions are crucial in the process of information transmission and integration in the central nervous system (CNS). These ions participate not only in intracellular mechanisms but also in intercellular processes. The changes in the concentration of Ca2 + ions modulate synaptic transmission, whereas neuronal activity induces calcium ion waves. Disturbed calcium homeostasis is thought to be one of the main features in the pathophysiology of Alzheimer's disease (AD), and AD pathogenesis is closely connected to Ca2 + signaling pathways. The effects of changes in neuronal Ca2 + are mediated by neuronal calcium sensor (NCS) proteins. It has been revealed that NCS proteins, with special attention to visinin-like protein 1 (VILIP-1), might have a connection to the etiology of AD. In the CNS, VILIP-1 influences the intracellular neuronal signaling pathways involved in synaptic plasticity, such as cyclic nucleotide cascades and nicotinergic signaling. This particular protein is implicated in calcium-mediated neuronal injury as well. VILIP-1 also participates in the pathological mechanisms of altered Ca2 + homeostasis, leading to neuronal loss. These findings confirm the utility of VILIP-1 as a useful biomarker of neuronal injury. Moreover, VILIP-1 plays a vital role in linking calcium-mediated neurotoxicity and AD-type pathological changes. The disruption of Ca2 + homeostasis caused by AD-type neurodegeneration may result in the damage of VILIP-1-containing neurons in the brain, leading to increased cerebrospinal fluid levels of VILIP-1. Thus, the aim of this overview is to describe the relationships of the NCS protein VILIP-1 with the pathogenetic factors of AD and neurodegenerative processes, as well as its potential clinical usefulness as a biomarker of AD. Moreover, we describe the current and probable therapeutic strategies for AD, targeting calcium-signaling pathways and VILIP-1.

Our findings suggest that VILIP-1 may play a role in the AD pathophysiology and is a good candidate for dynamic biomarker of AD, although this issue requires further investigation.

C-X-C motif chemokine 8 (CXCL-8), known as interleukin-8, is a pro-inflammatory cytokine which acts as a chemotactic factor, mainly for leukocytes. CXCL-8 is produced by malignant cells, and therefore it can stimulate the growth and progression of various neoplasms, including oesophageal cancer (OC). The aim of the current study was to measure serum concentrations of chemokine CXCL-8 in OC patients and establish whether this protein might be considered a potential candidate for a tumor marker in the diagnosis and progression of OC. The study included 50 OC subjects (32 patients with squamous cell carcinoma of oesophagus—OSCC, 18 patients with adenocarcinoma—OAC) and 26 healthy volunteers. Serum CXCL-8 concentrations were measured using immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetric method, while classical tumor marker levels were measured using chemiluminescent immunoassay. CXCL-8 concentrations were significantly higher in OC patients compared to healthy controls. We demonstrated significant differences between CXCL-8 concentrations and depth of tumor invasion (T factor) in OC patients and OSCC subgroup. In addition, CXCL-8 levels were found to correlate positively with T factor and CRP concentrations. The diagnostic sensitivity, negative predictive value and the area under ROC curve (AUC) of CXCL-8 were higher than those of classical tumor markers. Our findings suggest the potential usefulness of CXCL-8 in the diagnosis and progression of OC. However, due to the non-specific nature of this chemokine, further research is needed to clarify the usefulness of CXCL-8 as a tumor marker of OC.