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Circulating Biomarkers for the Diagnosis of Neurobiological Diseases 2.0
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Circulating Biomarkers for the Diagnosis of Neurobiological Diseases 2.0

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: 20 February 2025 | Viewed by 6210

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

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Keywords

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

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Related Special Issue

Published Papers (4 papers)

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Research

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18 pages, 3677 KiB  
Article
Differential Protein Expression in Extracellular Vesicles Defines Treatment Responders and Non-Responders in Multiple Sclerosis
by Gabriel Torres Iglesias, MariPaz López-Molina, Lucía Botella, Fernando Laso-García, Beatriz Chamorro, Mireya Fernández-Fournier, Inmaculada Puertas, Susana B. Bravo, Elisa Alonso-López, Exuperio Díez-Tejedor, María Gutiérrez-Fernández and Laura Otero-Ortega
Int. J. Mol. Sci. 2024, 25(19), 10761; https://doi.org/10.3390/ijms251910761 - 6 Oct 2024
Viewed by 1261
Abstract
Multiple sclerosis (MS) remains the leading cause of neurological disability among young adults worldwide, underscoring the urgent need to define the best therapeutic strategy. Recent advances in proteomics have deepened our understanding of treatment mechanisms and revealed promising biomarkers for predicting therapeutic outcomes. [...] Read more.
Multiple sclerosis (MS) remains the leading cause of neurological disability among young adults worldwide, underscoring the urgent need to define the best therapeutic strategy. Recent advances in proteomics have deepened our understanding of treatment mechanisms and revealed promising biomarkers for predicting therapeutic outcomes. This study focuses on the identification of a protein profile of circulating extracellular vesicles (EVs) derived from neurons, oligodendrocytes, and B and T cells able to differentiate treatment responders and non-responders in 80 patients with MS. In the patients who responded to treatment, T cell-derived EVs were enriched in LV151, a protein involved in the promotion of anti-inflammatory cytokines, whereas Bcell-derived EVs showed elevated PSMD6 and PTPRC, related to immunoproteasome function. Oligodendrocyte- and neuron-derived EVs showed upregulated CO6A1 and COEA1, involved in extracellular matrix reorganisation, as well as LAMA5, NonO, SPNT, and NCAM, which are critical for brain repair. In contrast, non-responders showed higher levels of PSMD7 and PRS10 from B cell-derived EVs, associated with DNA damage, and increased levels of PERM and PERL from T cell-derived EVs, linked to nuclear factor kappa B activation and drug-resistant proteins such as HS90A and RASK. These findings highlight a distinct panel of proteins in EVs that could serve as an early indicator of treatment efficacy in MS. Full article
(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases 2.0)
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14 pages, 1756 KiB  
Article
Diagnostic and Prognostic Value of Plasma GFAP in Sporadic Creutzfeldt–Jakob Disease in the Clinical Setting of Rapidly Progressive Dementia
by Giuseppe Mario Bentivenga, Simone Baiardi, Andrea Mastrangelo, Corrado Zenesini, Angela Mammana, Marcello Rossi, Barbara Polischi, Sabina Capellari and Piero Parchi
Int. J. Mol. Sci. 2024, 25(10), 5106; https://doi.org/10.3390/ijms25105106 - 8 May 2024
Viewed by 1310
Abstract
The diagnostic and prognostic value of plasma glial fibrillary acidic protein (pl-GFAP) in sporadic Creutzfeldt–Jakob disease (sCJD) has never been assessed in the clinical setting of rapidly progressive dementia (RPD). Using commercially available immunoassays, we assayed the plasma levels of GFAP, tau (pl-tau), [...] Read more.
The diagnostic and prognostic value of plasma glial fibrillary acidic protein (pl-GFAP) in sporadic Creutzfeldt–Jakob disease (sCJD) has never been assessed in the clinical setting of rapidly progressive dementia (RPD). Using commercially available immunoassays, we assayed the plasma levels of GFAP, tau (pl-tau), and neurofilament light chain (pl-NfL) and the CSF total tau (t-tau), 14-3-3, NfL, phospho-tau181 (p-tau), and amyloid-beta isoforms 42 (Aβ42) and 40 (Aβ40) in sCJD (n = 132) and non-prion RPD (np-RPD) (n = 94) patients, and healthy controls (HC) (n = 54). We also measured the CSF GFAP in 67 sCJD patients. Pl-GFAP was significantly elevated in the sCJD compared to the np-RPD and HC groups and affected by the sCJD subtype. Its diagnostic accuracy (area under the curve (AUC) 0.760) in discriminating sCJD from np-RPD was higher than the plasma and CSF NfL (AUCs of 0.596 and 0.663) but inferior to the 14-3-3, t-tau, and pl-tau (AUCs of 0.875, 0.918, and 0.805). Pl-GFAP showed no association with sCJD survival after adjusting for known prognostic factors. Additionally, pl-GFAP levels were associated with 14-3-3, pl-tau, and pl-NfL but not with CSF GFAP, Aβ42/Aβ40, and p-tau. The diagnostic and prognostic value of pl-GFAP is inferior to established neurodegeneration biomarkers. Nonetheless, pl-GFAP noninvasively detects neuroinflammation and neurodegeneration in sCJD, warranting potential applications in disease monitoring. Full article
(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases 2.0)
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Review

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14 pages, 872 KiB  
Review
Neuroinflammatory Biomarkers in Alzheimer’s Disease: From Pathophysiology to Clinical Implications
by Fausto Roveta, Lucrezia Bonino, Elisa Maria Piella, Innocenzo Rainero and Elisa Rubino
Int. J. Mol. Sci. 2024, 25(22), 11941; https://doi.org/10.3390/ijms252211941 - 6 Nov 2024
Viewed by 617
Abstract
The identification of neuroinflammation as a critical factor in Alzheimer’s disease (AD) has expanded the focus of research beyond amyloid-β and tau pathology. The neuroinflammatory fluid biomarkers GFAP, sTREM2, and YKL-40 have gained attention for their potential in early detection and monitoring of [...] Read more.
The identification of neuroinflammation as a critical factor in Alzheimer’s disease (AD) has expanded the focus of research beyond amyloid-β and tau pathology. The neuroinflammatory fluid biomarkers GFAP, sTREM2, and YKL-40 have gained attention for their potential in early detection and monitoring of disease progression. Plasma GFAP has demonstrated promise in predicting the conversion from mild cognitive impairment to AD dementia, while sTREM2 highlights microglial activation, although there are conflicting results regarding its dynamics in AD pathogenesis. Advanced imaging techniques, such as PET tracers targeting TSPO and MAO-B, have also been developed to visualize glial activation in vivo, offering spatial and temporal insights into neuroinflammatory processes. However, the clinical implementation of these biomarkers faces challenges due to their lack of specificity, as many of them can be elevated in other conditions. Therapeutic strategies targeting neuroinflammation are emerging, with TREM2-targeting therapies and antidiabetic drugs like GLP-1 receptor agonists showing potential in modulating microglial activity. Nevertheless, the complexity of neuroinflammation, which encompasses both protective and harmful responses, necessitates further research to fully unravel its role and optimize therapeutic approaches for AD. Full article
(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases 2.0)
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16 pages, 1064 KiB  
Review
Tau, Glial Fibrillary Acidic Protein, and Neurofilament Light Chain as Brain Protein Biomarkers in Cerebrospinal Fluid and Blood for Diagnosis of Neurobiological Diseases
by Yongkyu Park, Nirajan KC, Alysta Paneque and Peter D. Cole
Int. J. Mol. Sci. 2024, 25(12), 6295; https://doi.org/10.3390/ijms25126295 - 7 Jun 2024
Cited by 5 | Viewed by 2488
Abstract
Neurological damage is the pathological substrate of permanent disability in various neurodegenerative disorders. Early detection of this damage, including its identification and quantification, is critical to preventing the disease’s progression in the brain. Tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain [...] Read more.
Neurological damage is the pathological substrate of permanent disability in various neurodegenerative disorders. Early detection of this damage, including its identification and quantification, is critical to preventing the disease’s progression in the brain. Tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), as brain protein biomarkers, have the potential to improve diagnostic accuracy, disease monitoring, prognostic assessment, and treatment efficacy. These biomarkers are released into the cerebrospinal fluid (CSF) and blood proportionally to the degree of neuron and astrocyte damage in different neurological disorders, including stroke, traumatic brain injury, multiple sclerosis, neurodegenerative dementia, and Parkinson’s disease. Here, we review how Tau, GFAP, and NfL biomarkers are detected in CSF and blood as crucial diagnostic tools, as well as the levels of these biomarkers used for differentiating a range of neurological diseases and monitoring disease progression. We also discuss a biosensor approach that allows for the real-time detection of multiple biomarkers in various neurodegenerative diseases. This combined detection system of brain protein biomarkers holds significant promise for developing more specific and accurate clinical tools that can identify the type and stage of human neurological diseases with greater precision. Full article
(This article belongs to the Special Issue Circulating Biomarkers for the Diagnosis of Neurobiological Diseases 2.0)
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