Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Circulating Biomarkers for the Diagnosis of Neurobiological Diseases

Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 11943

Share This Special Issue

Special Issue Editor

Dr. Yasemin M. Akay

E-Mail Website
Guest Editor

Department of Biomedical Engineering, University of Houston, Houston, TX 77204-5060, USA
Interests: coronary artery disease; stent; noninvasive monitoring; nonlinear dynamics analysis; approximate entropy; 3D co-culture; glioblastoma; astrocytes; tumor microenvironment; PEGDA; addiction; cancer research; data science in medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Neurobiological diseases represent a major health problem. Even before COVID-19, they were the second leading cause of death and the leading cause of disability all over the world. Since the beginning of the pandemic, the rise in many neurobiological symptoms and the aggravation of current neurobiological conditions, particularly in the elderly, due to COVID-19 have been observed. As of now, many people are suffering due to a condition called long COVID-19, which has deteriorating effects on neurobiological systems in particular.

The above being the case, newer and more precise methods are needed for the diagnosis and classification of the stages of neurobiological diseases. Recently, scientiﬁc research has focused on novel circulating biomarkers, which are biological indicators that objectively measure and evaluate physiological and/or pathophysiological parameters or pharmacological responses to therapeutics.

Current research on circulating microRNAs (miRNAs) have suggested that they play a crucial role in regulating gene expression, and they have become an intensely studied research topic because of their close connection with the development of neurobiological diseases. Circulating miRNAs are believed to be potential biomarkers for various neurobiological diseases due to their valuable characteristics, including their sustentation, reliability, and high abundance in body fluids.

In this Special Issue, we focus on circulating biomarkers for the diagnosis and reliable detection of the diﬀerent stages of neurobiological diseases, their diverseness, and their pathogenesis, thereby designing targeted tailored treatments and predicting response outcomes to interventions.

Dr. Yasemin M. Akay
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

circulating miRNAs
differently expressed genes
long COVID-19
neurobiological diseases
mesenchymal stem cells
circulating pasma exosomes
neuropathogenesis
proteomic analysis

Related Special Issue

Circulating Biomarkers for the Diagnosis of Neurobiological Diseases—2nd Edition in International Journal of Molecular Sciences

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

19 pages, 2715 KiB

Open AccessArticle

Plasma miR-203a-3p as a Novel Predictor of Dementia in Patients with Parkinson’s Disease

by Ya-Fang Hsu, Shau-Ping Lin, Yung-Tsai Chu, Yi-Tzang Tsai, Jing-Wen Huang, Frederick Kin Hing Phoa and Ruey-Meei Wu

Int. J. Mol. Sci. 2024, 25(6), 3554; https://doi.org/10.3390/ijms25063554 - 21 Mar 2024

Viewed by 720

Abstract

The early detection of cognitive decline in Parkinson’s disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = −0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

12 pages, 534 KiB

Open AccessArticle

Effect of DIO2 Gene Polymorphism on Thyroid Hormone Levels and Its Correlation with the Severity of Schizophrenia in a Pakistani Population

by Farina Hanif, Quratulain Amir and Washdev Washdev

Int. J. Mol. Sci. 2024, 25(3), 1915; https://doi.org/10.3390/ijms25031915 - 05 Feb 2024

Viewed by 836

Abstract

Low levels of triiodothyronine (T3) in the brain lead to increased dopamine receptor sensitivity, potentially resulting in schizophrenia. Iodothyronine deiodinase 2 (DIO2) is the only enzyme which converts tetraiodothyronine (T4) to T3 in the brain. DIO2 polymorphism of rs225014 results in the expression of non-functioning DIO2. Therefore, this study aimed to investigate the association of rs255014 with schizophrenia and its impact on thyroid hormone levels. This study included 150 schizophrenia cases and 150 controls. DNA was extracted from blood and subjected to PCR and amplicon sequencing. Serum thyroid profiles were determined using chemiluminescent magnetic microparticle immunoassay. Statistical analyses involved independent sample t-tests, Chi-square, and Pearson’s correlation tests. The results revealed a higher frequency of the reference genotype (TT) in controls compared to cases (p < 0.05). However, rs225014 did not influence serum thyroid levels or the severity of schizophrenia (p > 0.05). Interestingly, control subjects exhibited significantly higher T3 levels (p < 0.001) than cases. Regardless of the genotype (TT or CC), the control group had higher mean T3 levels than the corresponding case group (p < 0.05). In conclusion, rs225014 is associated with schizophrenia and has no effect on serum thyroid hormone levels. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

15 pages, 1247 KiB

Open AccessArticle

Neurofilament Light Chain Protein in Plasma and Extracellular Vesicles Is Associated with Minimal Hepatic Encephalopathy and Responses to Rifaximin Treatment in Cirrhotic Patients

by Alessandra Fiorillo, Juan José Gallego, Franc Casanova-Ferrer, Amparo Urios, María-Pilar Ballester, Teresa San Miguel, Javier Megías, Elena Kosenko, Joan Tosca, Maria-Pilar Rios, Desamparados Escudero-García and Carmina Montoliu

Int. J. Mol. Sci. 2023, 24(19), 14727; https://doi.org/10.3390/ijms241914727 - 29 Sep 2023

Cited by 1 | Viewed by 877

Abstract

Neurofilament light chain protein (NfL) levels reflect neuronal damage in several neurological diseases and have been proposed as a possible biomarker. Plasma extracellular vesicles (EVs) could play an important role as mediators of the inflammatory changes associated with inducing minimal hepatic encephalopathy (MHE) in cirrhotic patients. This study investigated the association of NfL levels in plasma and EVs with the presence of MHE in cirrhotic patients, and with responses to rifaximin treatment. The NfL levels in plasma and EVs were assessed in 71 patients with liver cirrhosis (40 with MHE and 31 without MHE) and 26 controls. A total of 31 patients with MHE received rifaximin treatment. We examined changes in NfL levels in plasma and EVs before and after 6 months of rifaximin treatment. The NfL measures were correlated with cognitive alterations and plasma inflammatory cytokines. MHE patients showed increased plasma levels of NfL, which were reverted after rifaximin treatment in patients who responded to treatment. The NfL content in EVs also showed a reversal pattern in MHE patients treated with rifaximin. In multivariable analyses, NfL levels were independently associated with the presence of MHE. We also showed that patients with high levels of both ammonia and fractalkine had significantly higher NfL levels than patients with low levels of least one of these parameters. Rifaximin treatment in MHE patients showed promising results in improving axonal damage, suggesting that rifaximin may have therapeutic benefits against disease progression in MHE. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Graphical abstract

12 pages, 2203 KiB

Open AccessArticle

Antibody Content against Epstein–Barr Virus in Blood Extracellular Vesicles Correlates with Disease Activity and Brain Volume in Patients with Relapsing–Remitting Multiple Sclerosis

by Mireya Fernández-Fournier, MariPaz López-Molina, Gabriel Torres Iglesias, Lucía Botella, Beatriz Chamorro, Fernando Laso-García, Inmaculada Puertas, Antonio Tallón Barranco, Laura Otero-Ortega, Ana Frank-García and Exuperio Díez-Tejedor

Int. J. Mol. Sci. 2023, 24(18), 14192; https://doi.org/10.3390/ijms241814192 - 16 Sep 2023

Cited by 1 | Viewed by 985

Abstract

We aimed to analyze whether EVs carry antibodies against EBV antigens and the possibility that they could serve as diagnostic and disease activity blood biomarkers in RRMS. This was a prospective and observational study including patients with RRMS with active and inactive disease and healthy controls. Blood EVs were isolated by precipitation. Titers of antibodies against nuclear (anti-EBNA1) and capsid (anti-VCA) EBV antigens in EVs and in plasma, as well as content of myelin antibodies in EVs were determined by ELISA. An exploratory analysis of correlations with clinical and radiological data was performed. Patients with RRMS had higher titers of anti-VCA inside EVs and free in plasma than healthy controls. Patients with active disease showed higher levels of anti-EBNA1 in EVs, but not in plasma, than patients with inactive disease. EV anti-VCA levels correlated with disease duration and with decreased brain volume structures—total brain, white matter, gray matter, cerebellum, hippocampus, —but not with T2/FLAIR lesion volume or EDSS, SDMT, or 9HPT. In addition, EV anti-VCA correlated with EV anti-MBP. The anti-VCA and anti-EBNA1 content in EVs could represent diagnostic and disease activity blood biomarkers, respectively, in RRMS. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

16 pages, 1512 KiB

Open AccessArticle

Early Alzheimer’s Disease Screening Approach Using Plasma Biomarkers

by Lourdes Álvarez-Sánchez, Carmen Peña-Bautista, Laura Ferré-González, Laura Cubas, Angel Balaguer, Bonaventura Casanova-Estruch, Miguel Baquero and Consuelo Cháfer-Pericás

Int. J. Mol. Sci. 2023, 24(18), 14151; https://doi.org/10.3390/ijms241814151 - 15 Sep 2023

Viewed by 899

Abstract

Alzheimer’s disease (AD) is the most prevalent dementia, but it shows similar initial symptoms to other neurocognitive diseases (Lewy body disease (LBD) and frontotemporal dementia (FTD)). Thus, the identification of reliable AD plasma biomarkers is required. The aim of this work is to evaluate the use of a few plasma biomarkers to develop an early and specific AD screening method. Plasma p-Tau181, neurofilament light (NfL), and glial fibrillary acid protein (GFAP) were determined by Single Molecule Assay (SIMOA^® Quanterix, Billerica, MA, USA) in patients with mild cognitive impairment due to AD (MCI-AD, n = 50), AD dementia (n = 10), FTD (n = 20), LBD (n = 5), and subjective cognitive impairment (SCI (n = 21)). Plasma p-Tau181 and GFAP showed the highest levels in AD dementia, and significant correlations with clinical AD characteristics; meanwhile, NfL showed the highest levels in FTD, but no significant correlations with AD. The partial least squares (PLS) diagnosis model developed between the AD and SCI groups showed good accuracy with a receiver operating characteristic (ROC) area under curve (AUC) of 0.935 (CI 95% 0.87–0.98), sensitivity of 86%, and specificity of 88%. In a first screen, NfL plasma levels could identify FTD patients among subjects with cognitive impairment. Then, the developed PLS model including p-Tau181 and GFAP levels could identify AD patients, constituting a simple, early, and specific diagnosis approach. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 1240 KiB

Open AccessReview

Long COVID: Molecular Mechanisms and Detection Techniques

by Adela Constantinescu-Bercu, Andrei Lobiuc, Olga Adriana Căliman-Sturdza, Radu Cristian Oiţă, Monica Iavorschi, Naomi-Eunicia Pavăl, Iuliana Șoldănescu, Mihai Dimian and Mihai Covasa

Int. J. Mol. Sci. 2024, 25(1), 408; https://doi.org/10.3390/ijms25010408 - 28 Dec 2023

Viewed by 2778

Abstract

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

17 pages, 875 KiB

Open AccessReview

miRNAs: Targets to Investigate Herpesvirus Infection Associated with Neurological Disorders

by Vanessa Cristine de Souza Carneiro, Luciane Almeida Amado Leon and Vanessa Salete de Paula

Int. J. Mol. Sci. 2023, 24(21), 15876; https://doi.org/10.3390/ijms242115876 - 01 Nov 2023

Viewed by 848

Abstract

Herpesvirus is associated with various neurological disorders and a specific diagnosis is associated with a better prognosis. MicroRNAs (miRNAs) are potential diagnostic and prognostic biomarkers of neurological diseases triggered by herpetic infection. In this review, we discuss miRNAs that have been associated with neurological disorders related to the action of herpesviruses. Human miRNAs and herpesvirus-encoded miRNAs were listed and discussed. This review article will be valuable in stimulating the search for new diagnostic and prognosis alternatives and understanding the role of these miRNAs in neurological diseases triggered by herpesviruses. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

20 pages, 4826 KiB

Open AccessReview

Blood Biomarkers as Prognostic Indicators for Neurological Injury in COVID-19 Patients: A Systematic Review and Meta-Analysis

by Zhiwei Huang, Kassahun Haile, Lealem Gedefaw, Benson Wui-Man Lau, Ling Jin, Shea Ping Yip and Chien-Ling Huang

Int. J. Mol. Sci. 2023, 24(21), 15738; https://doi.org/10.3390/ijms242115738 - 30 Oct 2023

Viewed by 1077

Abstract

Coronavirus disease 2019 (COVID-19) has been linked to various neurological complications. This meta-analysis assessed the relationship between glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels in the blood and neurological injury in COVID-19 patients. A comprehensive search of various databases was conducted until 18 August 2023, to find studies reporting GFAP and NfL blood levels in COVID-19 patients with neurological complications. GFAP and NfL levels were estimated between COVID-19 patients and healthy controls, and meta-analyses were performed using RevMan 5.4 software for analysis. In the 21 collected studies, it was found that COVID-19 patients had significantly higher levels of pooled GFAP (SMD = 0.52; 95% CI: 0.31, 0.73; p ≤ 0.001) and NfL (SMD = 0.60; 95% CI: 0.37, 0.82; p ≤ 0.001) when compared to the healthy controls. The pooled GFAP (SMD = 0.86; 95% CI: 0.26, 1.45; p ≤ 0.01) and NfL (SMD = 0.87; 95% CI: 0.48, 1.26; p ≤ 0.001) were significantly higher in non-survivors. These findings indicate a significant association between COVID-19 severity and elevated levels of GFAP and NfL, suggesting that GFAP and NfL could serve as potential diagnostic and prognostic markers for the early detection and monitoring of COVID-19-related neurological injuries. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

16 pages, 1775 KiB

Open AccessReview

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation

by Dénes Tóth, Gábor Simon and Dóra Reglődi

Int. J. Mol. Sci. 2023, 24(20), 15063; https://doi.org/10.3390/ijms242015063 - 11 Oct 2023

Viewed by 705

Abstract

Sudden infant death syndrome (SIDS) represents a significant cause of post-neonatal mortality, yet its underlying mechanisms remain unclear. The triple-risk model of SIDS proposes that intrinsic vulnerability, exogenous triggers, and a critical developmental period are required for SIDS to occur. Although case–control studies have identified potential risk factors, no in vivo model fully reflects the complexities observed in human studies. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide with diverse physiological functions, including metabolic and thermal regulation, cardiovascular adaptation, breathing control, stress responses, sleep–wake regulation and immunohomeostasis, has been subject to early animal studies, which revealed that the absence of PACAP or its specific receptor (PAC1 receptor: PAC1R) correlates with increased neonatal mortality similar to the susceptible period for SIDS in humans. Recent human investigations have further implicated PACAP and PAC1R genes as plausible contributors to the pathomechanism of SIDS. This mini-review comprehensively synthesizes all PACAP-related research from the perspective of SIDS and proposes that PACAP deficiency might offer a promising avenue for studying SIDS. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Figure 1

29 pages, 2348 KiB

Open AccessReview

Morphometric and Nanomechanical Screening of Peripheral Blood Cells with Atomic Force Microscopy for Label-Free Assessment of Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

by Stefka G. Taneva, Svetla Todinova and Tonya Andreeva

Int. J. Mol. Sci. 2023, 24(18), 14296; https://doi.org/10.3390/ijms241814296 - 19 Sep 2023

Viewed by 1259

Abstract

Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today’s society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs—Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD. Full article

(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases)

► Show Figures

Journal Menu

Journal Browser

Circulating Biomarkers for the Diagnosis of Neurobiological Diseases

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Related Special Issue

Published Papers (10 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI