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The Role of Cerebrospinal Fluid and Blood Biomarkers in Neurological Diseases

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 (30 November 2022) | Viewed by 11838

Special Issue Editors

Dr. Samir Abu Rumeileh

E-Mail Website
Guest Editor
Department of Neurology, Martin-Luther-University of Halle-Wittenberg, Halle (Saale), Germany
Interests: biomarkers; prion disease; Creutzfeldt-Jakob disease; Alzheimer's disease; COVID-19
Prof. Dr. Petra Steinacker

E-Mail Website
Guest Editor
Department of Neurology, Universitat Ulm, Ulm, Germany
Interests: CSF; biomarker
Dr. Tommaso Schirinzi

E-Mail Website
Guest Editor
Department of Systems Medicine, University of Roma Tor Vergata, Rome, Italy
Interests: Parkinson’s disease; movement disorders; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Piero Parchi

E-Mail Website
Guest Editor
Department of Experimental Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
Interests: prion diseases; CSF biomarkers for neurodegenerative diseases

Special Issue Information

Dear Colleagues,

In recent decades, the discovery and validation of cerebrospinal fluid (CSF) biomarkers have represented a substantial advance in the approach of most neurological diseases. Recently, the introduction of highly sensitive immunoassays has also offered the possibility to obtain rapid and reproducible measurements of analytes from blood samples, opening new perspectives for the large implementation of biomarkers in the clinical setting. From a biological point of view, currently available markers reflect distinct and often interrelated pathophysiological mechanisms affecting the central and/or peripheral nervous system, such as neuronal damage, brain amyloidosis, neuroinflammation, synaptic loss, and other phenomena. So far, thousands of studies have investigated the diagnostic, prognostic, pharmacodynamic, and predictive potentials of biomarkers in neurodegenerative, neuroimmunological, neuroinfectious, genetic, cerebrovascular, neoplastic, and traumatic disorders.

We are pleased to announce a new Special Issue on “The Role of Cerebrospinal Fluid and Blood Biomarkers in Neurological Diseases”, which will provide a comprehensive update on the latest data in this field. Papers should focus on molecular biology aspects of CSF and blood biomarkers application. Papers focused only on clinical aspects of biomarker application could not be accepted.

Dr. Samir Abu Rumeileh
Prof. Dr. Petra Steinacker
Dr. Tommaso Schirinzi
Prof. Dr. Piero Parchi
Guest Editors

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

  • biomarkers
  • CSF
  • blood
  • neurodegeneration
  • neuroinflammation
  • diagnosis
  • prognosis

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Published Papers (4 papers)

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Research

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19 pages, 2576 KiB  
Article
Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases
by Kyoka Hoshi, Mayumi Kanno, Aya Goto, Yoshikazu Ugawa, Katsutoshi Furukawa, Hiroyuki Arai, Masakazu Miyajima, Koichi Takahashi, Kotaro Hattori, Keiichi Kan, Takashi Saito, Yoshiki Yamaguchi, Takashi Mitsufuji, Nobuo Araki and Yasuhiro Hashimoto
Int. J. Mol. Sci. 2023, 24(7), 6084; https://doi.org/10.3390/ijms24076084 - 23 Mar 2023
Viewed by 2195
Abstract
Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from [...] Read more.
Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from distinct cell types, their CSF levels have been found to be highly correlated with each other in cases of neurodegenerative disorders. The aim of this study was to examine these marker levels and their correlations in other neurological diseases, such as depression and schizophrenia, and disorders featuring abnormal CSF metabolism, including spontaneous intracranial hypotension (SIH) and idiopathic normal pressure hydrocephalus (iNPH). Brain-derived marker levels were found to be highly correlated with each other in the CSF of depression and schizophrenia patients. SIH is caused by CSF leakage, which is suspected to induce hypovolemia and a compensatory increase in CSF production. In SIH, the brain-derived markers were 2–3-fold higher than in other diseases, and, regardless of their diverse levels, they were found to be correlated with each other. Another abnormality of the CSF metabolism, iNPH, is possibly caused by the reduced absorption of CSF, which secondarily induces CSF accumulation in the ventricle; the excess CSF compresses the brain’s parenchyma to induce dementia. One potential treatment is a “shunt operation” to bypass excess CSF from the ventricles to the peritoneal cavity, leading to the attenuation of dementia. After the shunt operation, marker levels began to increase within a week and then further increased by 2–2.5-fold at three, six, and twelve months post-operation, at which point symptoms had gradually attenuated. Notably, the marker levels were found to be correlated with each other in the post-operative period. In conclusion, the brain-derived major glycoprotein markers were highly correlated in the CSF of patients with different neurological diseases, and their correlations were maintained even after surgical intervention. These results suggest that brain-derived proteins could be biomarkers of CSF production. Full article
(This article belongs to the Special Issue The Role of Cerebrospinal Fluid and Blood Biomarkers in Neurological Diseases)
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12 pages, 1850 KiB  
Article
Specific Cerebrospinal Fluid SerpinA1 Isoform Pattern in Alzheimer’s Disease
by Lorenzo Barba, Steffen Halbgebauer, Federico Paolini Paoletti, Giovanni Bellomo, Samir Abu-Rumeileh, Petra Steinacker, Federico Massa, Lucilla Parnetti and Markus Otto
Int. J. Mol. Sci. 2022, 23(13), 6922; https://doi.org/10.3390/ijms23136922 - 22 Jun 2022
Cited by 4 | Viewed by 1904
Abstract
SerpinA1 (α1-antitrypsin) is a soluble glycoprotein, the cerebrospinal fluid (CSF) isoforms of which showed disease-specific changes in neurodegenerative disorders that are still unexplored in Alz-heimer’s disease (AD). By means of capillary isoelectric focusing immunoassay, we investigated six serpinA1 isoforms in CSF samples of [...] Read more.
SerpinA1 (α1-antitrypsin) is a soluble glycoprotein, the cerebrospinal fluid (CSF) isoforms of which showed disease-specific changes in neurodegenerative disorders that are still unexplored in Alz-heimer’s disease (AD). By means of capillary isoelectric focusing immunoassay, we investigated six serpinA1 isoforms in CSF samples of controls (n = 29), AD-MCI (n = 29), AD-dem (n = 26) and Lewy body disease (LBD, n = 59) patients and correlated the findings with CSF AD core biomarkers (Aβ42/40 ratio, p-tau, t-tau). Four CSF serpinA1 isoforms were differently expressed in AD patients compared to controls and LBD patients, especially isoforms 2 and 4. AD-specific changes were found since the MCI stage and significantly correlated with decreased Aβ42/40 (p < 0.05) and in-creased p-tau and t-tau levels in CSF (p < 0.001). Analysis of serpinA1 isoform provided good di-agnostic accuracy in discriminating AD patients versus controls (AUC = 0.80) and versus LBD patients (AUC = 0.92), with best results in patients in the dementia stage (AUC = 0.97). SerpinA1 isoform expression is altered in AD patients, suggesting a common, albeit disease-specific, in-volvement of serpinA1 in most neurodegenerative disorders. Full article
(This article belongs to the Special Issue The Role of Cerebrospinal Fluid and Blood Biomarkers in Neurological Diseases)
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9 pages, 638 KiB  
Communication
Prodynorphin and Proenkephalin in Cerebrospinal Fluid of Sporadic Creutzfeldt–Jakob Disease
by Samir Abu-Rumeileh, Peggy Barschke, Patrick Oeckl, Simone Baiardi, Angela Mammana, Andrea Mastrangelo, Mhd Rami Al Shweiki, Petra Steinacker, Anna Ladogana, Sabina Capellari, Markus Otto and Piero Parchi
Int. J. Mol. Sci. 2022, 23(4), 2051; https://doi.org/10.3390/ijms23042051 - 12 Feb 2022
Cited by 4 | Viewed by 2120
Abstract
Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, [...] Read more.
Proenkephalin (PENK) and prodynorphin (PDYN) are endogenous opioid peptides mainly produced in the striatum and, to a lesser extent, in the cerebral cortex. Dysregulated metabolism and altered cerebrospinal fluid (CSF) levels of PENK and PDYN have been described in several neurodegenerative diseases. However, no study to date investigated these peptides in the CSF of sporadic Creutzfeldt–Jakob disease (sCJD). Using liquid chromatography-multiple reaction monitoring mass spectrometry, we evaluated the CSF PDYN- and PENK-derived peptide levels in 25 controls and 63 patients with sCJD belonging to the most prevalent molecular subtypes (MM(V)1, VV2 and MV2K). One of the PENK-derived peptides was significantly decreased in each sCJD subtype compared to the controls without a difference among subtypes. Conversely, PDYN-derived peptides were selectively decreased in the CSF of sCJD MV2K, a subtype with a more widespread overall pathology compared to the sCJD MM(V)1 and the VV2 subtypes, which we confirmed by semiquantitative analysis of cortical and striatal neuronal loss and astrocytosis. In sCJD CSF PENK and PDYN were associated with CSF biomarkers of neurodegeneration but not with clinical variables and showed a poor diagnostic performance. CSF PDYN and PENK-derived peptides had no significant diagnostic and prognostic values in sCJD; however, the distinct marker levels between molecular subtypes might help to better understand the basis of phenotypic heterogeneity determined by divergent neuronal targeting. Full article
(This article belongs to the Special Issue The Role of Cerebrospinal Fluid and Blood Biomarkers in Neurological Diseases)
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Review

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30 pages, 1159 KiB  
Review
Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings
by Chiara Demartini, Miriam Francavilla, Anna Maria Zanaboni, Sara Facchetti, Roberto De Icco, Daniele Martinelli, Marta Allena, Rosaria Greco and Cristina Tassorelli
Int. J. Mol. Sci. 2023, 24(6), 5334; https://doi.org/10.3390/ijms24065334 - 10 Mar 2023
Cited by 14 | Viewed by 4486
Abstract
In recent years, numerous efforts have been made to identify reliable biomarkers useful in migraine diagnosis and progression or associated with the response to a specific treatment. The purpose of this review is to summarize the alleged diagnostic and therapeutic migraine biomarkers found [...] Read more.
In recent years, numerous efforts have been made to identify reliable biomarkers useful in migraine diagnosis and progression or associated with the response to a specific treatment. The purpose of this review is to summarize the alleged diagnostic and therapeutic migraine biomarkers found in biofluids and to discuss their role in the pathogenesis of the disease. We included the most informative data from clinical or preclinical studies, with a particular emphasis on calcitonin gene-related peptide (CGRP), cytokines, endocannabinoids, and other biomolecules, the majority of which are related to the inflammatory aspects and mechanisms of migraine, as well as other actors that play a role in the disease. The potential issues affecting biomarker analysis are also discussed, such as how to deal with bias and confounding data. CGRP and other biological factors associated with the trigeminovascular system may offer intriguing and novel precision medicine opportunities, although the biological stability of the samples used, as well as the effects of the confounding role of age, gender, diet, and metabolic factors should be considered. Full article
(This article belongs to the Special Issue The Role of Cerebrospinal Fluid and Blood Biomarkers in Neurological Diseases)
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