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New Mechanisms and Therapeutics in Neurological Diseases 2.0

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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 June 2023) | Viewed by 44109

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Prof. Dr. Barbara Mroczko

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Department of Biochemical Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland
Interests: neurodegeneration; neuroinflammation; neurodegenerative diseases; neurodevelopmental disorders; tumor markers; specific proteins
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Special Issue Information

Dear Colleagues,

The term “neurodegenerative diseases” (NDs) collectively defines a group of pathological conditions of the nervous system characterized by the degeneration of neurons. This group of disorders includes different diseases leading to dementia or motor neuron disfunction, resulting in disability. Among them, Alzheimer’s (AD) and Parkinson’s diseases (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) have the greatest importance because of their devastating outcomes and enormous socio-economic impact. Although they have a variegated etiology, increasing role in their pathology is ascribed to neuroinflammatory processes. Neuroinflammation may affect not only neurons but also non-neuronal astrocytes and microglia cells, as well as immune cells entering the nervous system. These cells cooperate in both the damage and the repair of diseased brain tissue. The interactions between cells and the extracellular environment have emerged as new targets for the treatment of neurodegenerative disorders. However, the heterogeneity of the molecular and cellular mechanisms underlying these diseases hinders efforts at slowing down the progression of these diseases and their effective treatment. Moreover, the availability of biomarkers with appropriate sensitivity and specificity that could predict treatment success is very limited.

Inflammatory and infectious diseases of the central nervous system (CNS) may also be involved in the pathogenesis of neurodegeneration. Microbial infection has emerged as new risk factors for NDs, and new evidence supports the universal hypothesis that some bacteria, viruses, and even fungi could be involved not only in brain inflammation but also in neurodegeneration and dementia. The diagnosis of CNS infections and the identification of potential pathogenic pathways of these diseases are also topics of interest for this Special Issue, as well as the therapy and prevention of these diseases, including vaccination.

Studies on malignant primary brain tumors are also welcome. These tumors are a highly heterogeneous group of malignancies, with varied frequency within different age groups. Among them, glioblastoma is the most common and most malignant primary CNS tumor, affecting patients of all ages, from children to adults. Glioblastoma multiforme is an especially fatal tumor type, and only moderate progress has been achieved in its clinical management in the last years.

The goal of this Special Issue is to collect original research manuscripts, short communications, and reviews on the latest advances regarding new mechanisms of and therapeutics for neurological diseases, including neurodegeneration, neuroinflammation, and tumors of the central nervous system.

Topics of interest include (but are not limited to):

Biological mechanisms related to neurodegeneration, inflammation, and tumorigenesis within the central nervous system;
Neurodegenerative diseases as proteinopathies;
Relationship between neurodegeneration and inflammation;
New potential biomarkers of Alzheimer’s disease and other neurodegenerative diseases including mild cognitive impairment, multiple sclerosis, Parkinson’s disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington’s disease, and prion diseases;
Prognostic value of biomarkers of neurodegeneration in the conversion from mild cognitive impairment to fully symptomatic dementia;
Cytokines, chemokines, matrix metalloproteinases as prognostic factors in carcinogenesis of CNS malignant tumors;
Mediators of inflammation, chemokines, and their receptors as novel tumor markers in malignant tumors of the central nervous system in relation to the histological type of tumors;
Relationships between coronavirus diseas 2019 (Covid-19) and neurological diseases.

Prof. Dr. Barbara Mroczko
Guest Editor

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Keywords

neurodegeneration
neuroinflammation
neurodegenerative diseases
neurodevelopmental disorders
tumor markers
specific proteins

Related Special Issue

New Mechanisms and Therapeutics in Neurological Diseases 3.0 in International Journal of Molecular Sciences (2 articles)

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20 pages, 3687 KiB

Open AccessArticle

Real-Time PCR Quantification of 87 miRNAs from Cerebrospinal Fluid: miRNA Dynamics and Association with Extracellular Vesicles after Severe Traumatic Brain Injury

by Lara Valenčić Seršić, Vedrana Krušić Alić, Maša Biberić, Siniša Zrna, Tin Jagoić, Janja Tarčuković and Kristina Grabušić

Int. J. Mol. Sci. 2023, 24(5), 4751; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054751 - 01 Mar 2023

Cited by 3 | Viewed by 1988

Abstract

Severe traumatic brain injury (sTBI) is an intracranial damage triggered by external force, most commonly due to falls and traffic accidents. The initial brain injury can progress into a secondary injury involving numerous pathophysiological processes. The resulting sTBI dynamics makes the treatment challenging and prompts the improved understanding of underlying intracranial processes. Here, we analysed how extracellular microRNAs (miRNAs) are affected by sTBI. We collected thirty-five cerebrospinal fluids (CSF) from five sTBI patients during twelve days (d) after the injury and combined them into d1–2, d3–4, d5–6 and d7–12 CSF pools. After miRNA isolation and cDNA synthesis with added quantification spike-ins, we applied a real-time PCR-array targeting 87 miRNAs. We detected all of the targeted miRNAs, with totals ranging from several nanograms to less than a femtogram, with the highest levels found at d1–2 followed by decreasing levels in later CSF pools. The most abundant miRNAs were miR-451a, miR-16-5p, miR-144-3p, miR-20a-5p, let-7b-5p, miR-15a-5p, and miR-21-5p. After separating CSF by size-exclusion chromatography, most miRNAs were associated with free proteins, while miR-142-3p, miR-204-5p, and miR-223-3p were identified as the cargo of CD81-enriched extracellular vesicles, as characterised by immunodetection and tunable resistive pulse sensing. Our results indicate that miRNAs might be informative about both brain tissue damage and recovery after sTBI. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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12 pages, 841 KiB

Open AccessCommunication

Mechanisms of Susceptibility and Resilience to PTSD: Role of Dopamine Metabolism and BDNF Expression in the Hippocampus

by Vadim E. Tseilikman, Olga B. Tseilikman, Anton A. Pashkov, Irina S. Ivleva, Marina N. Karpenko, Vladislav A. Shatilov, Maxim S. Zhukov, Julia O. Fedotova, Marina V. Kondashevskaya, H. Fred Downey and Eugenia B. Manukhina

Int. J. Mol. Sci. 2022, 23(23), 14575; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314575 - 23 Nov 2022

Cited by 2 | Viewed by 1942

Abstract

Susceptibility and resilience to post-traumatic stress disorder (PTSD) are recognized, but their mechanisms are not understood. Here, the hexobarbital sleep test (HST) was used to elucidate mechanisms of PTSD resilience or susceptibility. A HST was performed in rats 30 days prior to further experimentation. Based on the HST, the rats were divided into groups: (1) fast metabolizers (FM; sleep duration < 15 min); (2) slow metabolizers (SM; sleep duration ≥ 15 min). Then the SM and FM groups were subdivided into stressed (10 days predator scent, 15 days rest) and unstressed subgroups. Among stressed animals, only SMs developed experimental PTSD, and had higher plasma corticosterone (CORT) than stressed FMs. Thus, resilience or susceptibility to PTSD was consistent with changes in glucocorticoid metabolism. Stressed SMs had a pronounced decrease in hippocampal dopamine associated with increased expressions of catecholamine-O-methyl-transferase and DA transporter. In stressed SMs, a decrease in monoaminoxidase (MAO) A was associated with increased expressions of hippocampal MAO-A and MAO-B. BDNF gene expression was increased in stressed FMs and decreased in stressed SMs. These results demonstrate relationships between the microsomal oxidation phenotype, CORT concentration, and anxiety, and they help further the understanding of the role of the liver–brain axis during PTSD. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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13 pages, 1652 KiB

Open AccessArticle

Acute Effects of Ocrelizumab Infusion in Multiple Sclerosis Patients

by Katja Akgün, Johanna Behrens, Dirk Schriefer and Tjalf Ziemssen

Int. J. Mol. Sci. 2022, 23(22), 13759; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213759 - 09 Nov 2022

Cited by 2 | Viewed by 2166

Abstract

B cell-depleting therapies such as ocrelizumab (OCR) are highly effective in people with multiple sclerosis (MS). Especially at treatment start and initial infusion, infusion-related reactions (IRR) are a common adverse event. The relevance of acute changes of cell-depleting therapies on peripheral immune compartments and routine lab testing is important for clinical practice. We systematically analyzed routine blood parameters, detailed blood immunophenotyping and serum cytokine profiles in 45 MS patients starting on OCR. Blood samples were collected before and after corticosteroid premedication and directly after each OCR infusion of the first three ocrelizumab infusions. Blood B cells were rapidly depleted and accompanied only by a mild cytokine release at the first OCR infusion. Cytokine release was not significantly detectable from a third application in line with decreasing IRRs. B cell depletion was accompanied by short-lived changes in other immune cell populations in number, activation and cytokine secretion after each OCR infusion. Standard lab parameters did not show any clinically relevant changes. Our data demonstrate only mild changes during the first OCR infusion, which are not present any more during long-term treatment. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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18 pages, 4534 KiB

Open AccessArticle

Rufinamide, a Triazole-Derived Antiepileptic Drug, Stimulates Ca²⁺-Activated K⁺ Currents While Inhibiting Voltage-Gated Na⁺ Currents

by Ming-Chi Lai, Sheng-Nan Wu and Chin-Wei Huang

Int. J. Mol. Sci. 2022, 23(22), 13677; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213677 - 08 Nov 2022

Cited by 2 | Viewed by 1527

Abstract

Rufinamide (RFM) is a clinically utilized antiepileptic drug that, as a triazole derivative, has a unique structure. The extent to which this drug affects membrane ionic currents remains incompletely understood. With the aid of patch clamp technology, we investigated the effects of RFM on the amplitude, gating, and hysteresis of ionic currents from pituitary GH₃ lactotrophs. RFM increased the amplitude of Ca²⁺-activated K⁺ currents (I_K(Ca)) in pituitary GH₃ lactotrophs, and the increase was attenuated by the further addition of iberiotoxin or paxilline. The addition of RFM to the cytosolic surface of the detached patch of membrane resulted in the enhanced activity of large-conductance Ca²⁺-activated K⁺ channels (BK_Ca channels), and paxilline reversed this activity. RFM increased the strength of the hysteresis exhibited by the BK_Ca channels and induced by an inverted isosceles-triangular ramp pulse. The peak and late voltage-gated Na⁺ current (I_Na) evoked by rapid step depolarizations were differentially suppressed by RFM. The molecular docking approach suggested that RFM bound to the intracellular domain of K_Ca1.1 channels with amino acid residues, thereby functionally affecting BK_Ca channels’ activity. This study is the first to present evidence that, in addition to inhibiting the I_Na, RFM effectively modifies the I_K(Ca), which suggests that it has an impact on neuronal function and excitability. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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8 pages, 2282 KiB

Open AccessArticle

Ella versus Simoa Serum Neurofilament Assessment to Monitor Treatment Response in Highly Active Multiple Sclerosis Patients

by Martin Nötzel, Luise Ina Werder, Tjalf Ziemssen and Katja Akgün

Int. J. Mol. Sci. 2022, 23(20), 12361; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012361 - 15 Oct 2022

Cited by 6 | Viewed by 2185

Abstract

The measurement of serum neurofilament light chain (sNfL) is of growing importance in the field of neurology. In the management of multiple sclerosis, it can serve as a useful marker to assess disease activity and treatment response. This paper compares two available methods, namely the Single Molecule Array (Simoa) and the Ella microfluid platform, to measure longitudinal sNfL levels of 42 highly active multiple sclerosis patients treated with alemtuzumab over a period of 36 months. In order to assess the methods agreement, Bland–Altman plots and Passing–Bablok regression were analyzed. Here, we show that despite the fact that Ella measures around 24% higher values than Simoa, both are equally suitable for longitudinal sNfL monitoring. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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14 pages, 1201 KiB

Open AccessArticle

Hemorrhagic Cerebral Insults and Secondary Takotsubo Syndrome: Findings in a Novel In Vitro Model Using Human Blood Samples

by Serge C. Thal, Manuel Smetak, Kentaro Hayashi and Carola Y. Förster

Int. J. Mol. Sci. 2022, 23(19), 11557; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911557 - 30 Sep 2022

Cited by 1 | Viewed by 1856

Abstract

Intracranial hemorrhage results in devastating forms of cerebral damage. Frequently, these results also present with cardiac dysfunction ranging from ECG changes to Takotsubo syndrome (TTS). This suggests that intracranial bleeding due to subarachnoid hemorrhage (SAH) disrupts the neuro–cardiac axis leading to neurogenic stress cardiomyopathy (NSC) of different degrees. Following this notion, SAH and secondary TTS could be directly linked, thus contributing to poor outcomes. We set out to test if blood circulation is the driver of the brain–heart axis by investigating serum samples of TTS patients. We present a novel in vitro model combining SAH and secondary TTS to mimic the effects of blood or serum, respectively, on blood–brain barrier (BBB) integrity using in vitro monolayers of an established murine model. We consistently demonstrated decreased monolayer integrity and confirmed reduced Claudin-5 and Occludin levels by RT-qPCR and Western blot and morphological reorganization of actin filaments in endothelial cells. Both tight junction proteins show a time-dependent reduction. Our findings highlight a faster and more prominent disintegration of BBB in the presence of TTS and support the importance of the bloodstream as a causal link between intracerebral bleeding and cardiac dysfunction. This may represent potential targets for future therapeutic inventions in SAH and TTS. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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21 pages, 825 KiB

Open AccessReview

Sex Differences in Brain Disorders

by Malgorzata Ziemka-Nalecz, Paulina Pawelec, Karolina Ziabska and Teresa Zalewska

Int. J. Mol. Sci. 2023, 24(19), 14571; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241914571 - 26 Sep 2023

Cited by 3 | Viewed by 2410

Abstract

A remarkable feature of the brain is its sexual dimorphism. Sexual dimorphism in brain structure and function is associated with clinical implications documented previously in healthy individuals but also in those who suffer from various brain disorders. Sex-based differences concerning some features such as the risk, prevalence, age of onset, and symptomatology have been confirmed in a range of neurological and neuropsychiatric diseases. The mechanisms responsible for the establishment of sex-based differences between men and women are not fully understood. The present paper provides up-to-date data on sex-related dissimilarities observed in brain disorders and highlights the most relevant features that differ between males and females. The topic is very important as the recognition of disparities between the sexes might allow for the identification of therapeutic targets and pharmacological approaches for intractable neurological and neuropsychiatric disorders. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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11 pages, 569 KiB

Open AccessReview

The Role of Cellular Prion Protein in Glioma Tumorigenesis Could Be through the Autophagic Mechanisms: A Narrative Review

by Daniele Armocida, Carla Letizia Busceti, Francesca Biagioni, Francesco Fornai and Alessandro Frati

Int. J. Mol. Sci. 2023, 24(2), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021405 - 11 Jan 2023

Cited by 1 | Viewed by 1713

Abstract

The carcinogenesis of glial tumors appears complex because of the many genetic and epigenetic phenomena involved. Among these, cellular prion protein (PrPC) is considered a key factor in cell-death resistance and important aspect implicated in tumorigenesis. Autophagy also plays an important role in cell death in various pathological conditions. These two cellular phenomena are related and share the same activation by specific alterations in the cellular microenvironment. Furthermore, there is an interdependence between autophagy and prion activity in glioma tumorigenesis. Glioma is one of the most aggressive known cancers, and the fact that such poorly studied processes as autophagy and PrPC activity are so strongly involved in its carcinogenesis suggests that by better understanding their interaction, more can be understood about its origin and treatment. Few studies in the literature relate these two cellular phenomena, much less try to explain their combined activity and role in glioma carcinogenesis. In this study, we explored the recent findings on the molecular mechanism and regulation pathways of autophagy, examining the role of PrPC in autophagy processes and how they may play a central role in glioma tumorigenesis. Among the many molecular interactions that PrP physiologically performs, it appears that processes shared with autophagy activity are those most implicated in glial tumor carcinogeneses such as activity on MAP kinases, PI3K, and mTOR. This work can be supportive and valuable as a basis for further future studies on this topic. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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20 pages, 2058 KiB

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Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers

by Daniela Meco, Giorgio Attinà, Stefano Mastrangelo, Pierluigi Navarra and Antonio Ruggiero

Int. J. Mol. Sci. 2023, 24(2), 1334; https://doi.org/10.3390/ijms24021334 - 10 Jan 2023

Cited by 18 | Viewed by 9515

Abstract

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood–brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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10 pages, 1150 KiB

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Alzheimer’s Disease—Biochemical and Psychological Background for Diagnosis and Treatment

by Bocwinska-Kiluk Beata, Jelski Wojciech, Kornhuber Johannes, Lewczuk Piotr and Mroczko Barbara

Int. J. Mol. Sci. 2023, 24(2), 1059; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021059 - 05 Jan 2023

Cited by 12 | Viewed by 4771

Abstract

There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer’s disease (AD) across the globe. This paper examines the biochemical and clinical outlook and the social implications of the condition in relation to psychological aspects that may indicate a direction for further interventions. There is a scarcity of research on the effectiveness of using various psychological aspects of AD, a disease characterized by a process of transition from health and independence to a dependent state with a progressive loss of memory and functional skills. The paper investigates the biochemical and psychological aspects of AD and their significance for improving quality of life for patients with this disease. Psychological interventions based on, among other factors, biochemical studies, are conducted to improve the emotional wellbeing of AD patients and may assist in slowing down the progression of the disease. To date, however, no effective methods of AD treatment have been established. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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34 pages, 1617 KiB

Open AccessReview

When Two Maladies Meet: Disease Burden and Pathophysiology of Stroke in Cancer

by Ming-Yee Sun and Sonu M. M. Bhaskar

Int. J. Mol. Sci. 2022, 23(24), 15769; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415769 - 12 Dec 2022

Cited by 2 | Viewed by 2889

Abstract

Stroke and cancer are disabling diseases with an enormous global burden, disproportionately affecting vulnerable populations and low- and middle-income countries. Both these diseases share common risk factors, which warrant concerted attention toward reshaping population health approaches and the conducting of fundamental studies. In this article, an overview of epidemiological trends in the prevalence and burden of cancer and stroke, underlying biological mechanisms and clinical risk factors, and various tools available for risk prediction and prognosis are provided. Finally, future recommendations for research and existing gaps in our understanding of pathophysiology. Further research must investigate the causes that predispose patients to an increased risk of stroke and/or cancer, as well as biomarkers that can be used to predict growing morbidity and mortality. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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12 pages, 349 KiB

Open AccessReview

Radiation as a Tool against Neurodegeneration—A Potential Treatment for Amyloidosis in the Central Nervous System

by Carina Marques Coelho, Lia Pereira, Pamela Teubig, Pedro Santos, Filipa Mendes, Sílvia Viñals, Daniel Galaviz and Federico Herrera

Int. J. Mol. Sci. 2022, 23(20), 12265; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012265 - 14 Oct 2022

Cited by 1 | Viewed by 2083

Abstract

Radiotherapy (RT) is a relatively safe and established treatment for cancer, where the goal is to kill tumoral cells with the lowest toxicity to healthy tissues. Using it for disorders involving cell loss is counterintuitive. However, ionizing radiation has a hormetic nature: it can have deleterious or beneficial effects depending on how it is applied. Current evidence indicates that radiation could be a promising treatment for neurodegenerative disorders involving protein misfolding and amyloidogenesis, such as Alzheimer’s or Parkinson’s diseases. Low-dose RT can trigger antioxidant, anti-inflammatory and tissue regeneration responses. RT has been used to treat peripheral amyloidosis, which is very similar to other neurodegenerative disorders from a molecular perspective. Ionizing radiation prevents amyloid formation and other hallmarks in cell cultures, animal models and pilot clinical trials. Although some hypotheses have been formulated, the mechanism of action of RT on systemic amyloid deposits is still unclear, and uncertainty remains regarding its impact in the central nervous system. However, new RT modalities such as low-dose RT, FLASH, proton therapy or nanoparticle-enhanced RT could increase biological effects while reducing toxicity. Current evidence indicates that the potential of RT to treat neurodegeneration should be further explored. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

19 pages, 1017 KiB

Open AccessReview

New Possibilities in the Therapeutic Approach to Alzheimer’s Disease

by Julia Doroszkiewicz and Barbara Mroczko

Int. J. Mol. Sci. 2022, 23(16), 8902; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23168902 - 10 Aug 2022

Cited by 14 | Viewed by 4598

Abstract

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. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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14 pages, 1076 KiB

Open AccessReview

Biomarkers for the Diagnosis of Alzheimer’s Disease in Clinical Practice: The Role of CSF Biomarkers during the Evolution of Diagnostic Criteria

by Maciej Dulewicz, Agnieszka Kulczyńska-Przybik, Piotr Mroczko, Johannes Kornhuber, Piotr Lewczuk and Barbara Mroczko

Int. J. Mol. Sci. 2022, 23(15), 8598; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158598 - 02 Aug 2022

Cited by 9 | Viewed by 3586

Abstract

Alzheimer’s disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer’s Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research. Full article

(This article belongs to the Special Issue New Mechanisms and Therapeutics in Neurological Diseases 2.0)

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