The gut microbiome has attracted increasing attention from researchers in recent years. The microbiota can have a specific and complex cross-talk with the host, particularly with the central nervous system (CNS), creating the so-called “gut–brain axis”. Communication between the gut, intestinal microbiota, and the brain involves the secretion of various metabolites such as short-chain fatty acids (SCFAs), structural components of bacteria, and signaling molecules. Moreover, an imbalance in the gut microbiota composition modulates the immune system and function of tissue barriers such as the blood–brain barrier (BBB). Therefore, the aim of this literature review is to describe how the gut–brain interplay may contribute to the development of various neurological disorders, combining the fields of gastroenterology and neuroscience. We present recent findings concerning the effect of the altered microbiota on neurodegeneration and neuroinflammation, including Alzheimer’s and Parkinson’s diseases, as well as multiple sclerosis. Moreover, the impact of the pathological shift in the microbiome on selected neuropsychological disorders, i.e., major depressive disorders (MDD) and autism spectrum disorder (ASD), is also discussed. Future research on the effect of balanced gut microbiota composition on the gut–brain axis would help to identify new potential opportunities for therapeutic interventions in the presented diseases.

The degeneration and dysfunction of neurons are key features of neurodegenerative diseases (NDs). Currently, one of the main challenges facing researchers and clinicians is the ability to obtain reliable diagnostic tools that will allow for the diagnosis of NDs as early as possible and the detection of neuronal dysfunction, preferably in the presymptomatic stage. Additionally, better tools for assessing disease progression in this group of disorders are also being sought. The ideal biomarker must have high sensitivity and specificity, be easy to measure, give reproducible results, and reflect the disease progression. Molecular biomarkers include miRNAs and extracellular microvesicles known as exosomes. They may be measured in two extracellular fluids of the highest importance in NDs, i.e., cerebrospinal fluid (CSF) and blood. The aim of the current review is to summarize the pathophysiology of the four most frequent NDs—i.e., Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)—as well as current progress in the research into miRNAs as biomarkers in these major neurodegenerative diseases. In addition, we discuss the possibility of using miRNA-based therapies in the treatment of neurodegenerative diseases, and present the limitations of this type of therapy.

Despite the fact that Alzheimer’s disease (AD) is the most common cause of dementia, after many years of research regarding this disease, there is no casual treatment. Regardless of the serious public health threat it poses, only five medical treatments for Alzheimer’s disease have been authorized, and they only control symptoms rather than changing the course of the disease. Numerous clinical trials of single-agent therapy did not slow the development of disease or improve symptoms when compared to placebo. Evidence indicates that the pathological alterations linked to AD start many years earlier than a manifestation of the disease. In this pre-clinical period before the neurodegenerative process is established, pharmaceutical therapy might prove invaluable. Although recent findings from the testing of drugs such as aducanumab are encouraging, they should nevertheless be interpreted cautiously. Such medications may be able to delay the onset of dementia, significantly lowering the prevalence of the disease, but are still a long way from having a clinically effective disease-modifying therapy.

: 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.

BackgroundAlzheimer's disease is a debilitating disease that leads to a disability of the patient and it is therefore interesting not only from a medical but also from a legal point of view. Despite progress in studies on pathological mechanisms underlying the Alzheimer's disease (AD) still remains incurable. One of the mechanisms responsible for the oligomerization / aggregation of misfolded or damaged proteins in AD may be dysfunction of the ubiquitin‐proteasome system (UPS), including the highly abundant neuronal enzyme ubiquitin carboxyl‐terminal hydrolase L1 (UCHL‐1). UCHL‐1 is involved in the regulation of proteasomal degradation of damaged proteins. The presence of UCH‐L1 was found in neurofibrillary tangles in the AD brain. The aim of the present study was to measure UCHL1 levels in the cerebrospinal fluid (CSF) patients with AD and evaluate a relationship between concentrations of UCHL1 and classical neurochemical dementia biomarkers.MethodThe concentrations of UCHL‐1 and classical AD biomarkers were measured in 30 subjects, including AD patients and individuals from control group by means of multiplexing assay.ResultThe CSF concentration of UCHL‐1 was significantly higher in AD group in comparison with cognitively normal individuals. Additionally, in the whole study group levels of UCHL‐1 correlated negatively with decreased concentration of Aβ 1‐42, MMSE. Furthermore, the significant relationship between UCHL‐1 and tau proteins was also revealed.ConclusionThe study suggest a potential role of UCHL‐1 protein in the pathology of AD and its potential usefulness as a candidate biomarker of AD, but these investigations need to be further confirmed.

Background: Alzheimer disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. The hallmarks underlying AD pathology are amyloid-β peptides, phosphorylated tau proteins and neuroinflammation. In vitro studies on cultured human microglia display a significant role of Interleukin 8 in neuroinflammation. Furthermore, CXCR2, IL-8 receptor, was found in dystrophic neurites which suggests connection to neuroinflammation in AD. Literature data indicates that gene polymorphism in IL-8 may affect the predisposition of Alzheimer's disease. It has been observed that IL-8 may increase Tau phosphorylation and subsequent NFTs formation. Thus, the aim of our research was to measure the concentration of IL-8 in cerebrospinal fluid of AD patients and non-demented controls. Moreover, we compare them to the concentrations of classical AD biomarkers, such as Aβ-42, Aβ-42/Aβ-40, Tau and pTau181. Method: The concentrations of IL-8 and classical AD biomarkers, such as Aβ-42, Aβ-42/Aβ-40, Tau and pTau181 were measured in cerebrospinal fluid (CSF) of 15 AD patients and 16 non-demented controls using immunoenzyme assays. Result: IL-8 concentrations were significantly higher in AD patients in comparison to non-demented controls. Moreover, increased CSF levels of IL-8 correlated with Aβ-42/Aβ-40 ratio, MMSE, Tau and pTau181 in the whole study group. Conclusion: Findings of our research suggest a potential role of IL-8 in pathology of AD. However, follow-up studies on larger study group are needed. Acknowledgement:The study was conducted with the use of equipment purchased by Medical University

Background: A complex relationship between the stromal cell-derived factor 1 (CXCL12) and dementia, including mild cognitive impairment (MCI) and Alzheimer's disease (AD) has been described in the literature. The chemokine CXCL12 regulates many functions of bone marrow-derived stem cells and has been implicated in neurogenesis as well as with the recruitment of brain resident and non-resident circulating cells towards sites of a lesion in the central nervous system. It has been suggested that dysregulation of the CXCL12/CXCR4 signaling pathway is involved in the pathologic process of cognitive impairment. Moreover, significantly changed expressions of the CXCL12 and CXCR4 were observed in AD patients' brains compared to the normal brain tissues of the healthy non-demented subjects. The purpose of the study was to evaluate the concentration of the CXCL12 in patients with early stage of dementia (MCI) and compare it with classical biomarkers for AD. Method:The study group included 34 subjects: 18 patients with AD and 16 controls without cognitive impairments. The cerebrospinal fluid (CSF) concentrations of tested proteins were measured with the use of ELISA method. Result:The CSF concentrations of CXCL12 were elevated in AD patients in comparison to non-demented controls. The increased levels of CXCL12 correlated with all CSF biomarkers (Aβ-42, Aβ-42/Aβ-40, Tau, pTau181), age and MMSE in the whole study group. Moreover, significant negative correlation between CXCL12 and MMSE in AD and control group was observed. Conclusion: It was established that CXCL12 might play role in the development of AD, although the question, whether this protein can be useful in diagnostic of dementia requires further examination on larger study group. Acknowledgment: The study was conducted with the use of equipment purchased by Medical University of Białystok

Background: Alzheimer Disease (AD) is a common neurodegenerative disorder which is the most widespread form of dementia in the world. The disease is characterized by amyloid-β peptides, phosphorylated tau proteins and neuroinflammation. Because of late manifestation of the disease, it is pivotal to find new biomarkers that can help detect AD in the earliest phases. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane endogenous glycoprotein involved in neuroinflammation. Recent studies have confirmed GPNMB presence in the microglia in AD patients brains, especially near amyloid-β plaques, although the exact role of this protein in AD is still not fully known. Furthermore, it has been observed that GPNMB may negatively influence secretion of proinflammatory cytokines form macrophages making this glycoprotein possibly protective to neuroinflammation. Thus, the purpose of our research was to measure the concentration of GPNMB in cerebrospinal fluid of AD patients and non-demented controls and compare with classical AD biomarkers. Method:The concentrations of GPNMB was measured in cerebrospinal fluid (CSF) of 17 AD patients and 17 non-demented controls using multiplexing method.Result: GPNMB concentrations were significantly higher in AD patients in comparison to non-demented controls. Moreover, increased CSF levels of GPNMB correlated positively with Tau, pTau181, age and negatively with Aβ-42, Aβ-42/Aβ-40 ratio and MMSE in the whole study group. Conclusion:Findings of our research suggest a potential role of GPNMB in pathology of AD. However, follow-up studies on larger study group are needed.