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Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease
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Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 17009

Special Issue Editor

Prof. Dr. Urszula Wojda

E-Mail Website
Guest Editor
Laboratory of Preclinical Testing of Higher Standard, Neurobiology Center, Nencki Institute of Experimental Biology, 3 Pasteur Str., 02-093 Warsaw, Poland
Interests: Alzheimer’s disease; molecular mechanisms of neurodegeneration; diagnostics; prognostics; biomarkers; machine learning; artificial intelligence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) is the most common cause of age-related dementia which affects 47 million individuals globally and, with a worldwide aging trend, is foreseen to increase to about 76 million in 2030. As causes of this complex neurodegenerative disease are not fully elucidated, no effective treatments for AD exist, making AD a growing socioeconomic burden among the major, currently unmet, health concerns.

Recently, a revolution in the concept and diagnostics of AD has occurred due to the introduction of biomarkers detected using brain imaging methods and immunoassays of cerebrospinal fluid (CSF). It was realized that molecular changes in AD precede the onset of clinical symptoms by decades and that, to overcome AD, early detection is critically important. Mounting research has therefore focused on the development of biomarkers in the brain, CSF and preferably in easily available tissues such as blood that could support early diagnosis and enable prognosis of AD in its asymptomatic and prodromal stages.

The aim of this Special Issue is to highlight these advancements by collecting original research articles as well as short or comprehensive reviews presenting the current developments in diagnostic and prognostic AD biomarkers in the brain, CSF, and blood. Original contributions on biomarker studies testing different hypotheses on AD pathogenesis and using various methodological approaches are welcome.

Prof. Urszula Wojda
Guest Editor

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Keywords

  • Alzheimer’s disease
  • Diagnostics
  • Prognostics
  • Biomarkers
  • Blood
  • Cerebrospinal fluid
  • Brain imaging
  • Proteomics
  • Genomics
  • Epigenomics
  • Noncoding RNA
  • MicroRNA
  • Machine learning
  • Artificial intelligence

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Published Papers (6 papers)

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Research

13 pages, 889 KiB  
Article
UCHL1 and Proteasome in Blood Serum in Relation to Dietary Habits, Concentration of Selected Antioxidant Minerals and Total Antioxidant Status among Patients with Alzheimer’s Disease
by Sylwia Bogdan, Anna Puścion-Jakubik, Katarzyna Klimiuk, Katarzyna Socha, Jan Kochanowicz and Ewa Gorodkiewicz
J. Clin. Med. 2022, 11(2), 412; https://doi.org/10.3390/jcm11020412 - 14 Jan 2022
Cited by 7 | Viewed by 2222
Abstract
Alzheimer’s disease (AD) is an incurable neurodegenerative disease. It is the most common form of dementia among the elderly population. So far, no effective methods of its treatment have been found. Research to better understand the mechanism of pathology may provide new methods [...] Read more.
Alzheimer’s disease (AD) is an incurable neurodegenerative disease. It is the most common form of dementia among the elderly population. So far, no effective methods of its treatment have been found. Research to better understand the mechanism of pathology may provide new methods for early diagnosis. This, in turn, could enable early intervention that could slow or halt disease progression and improve patients’ quality of life. Therefore, minimally invasive markers, including serum-based markers, are being sought to improve the diagnosis of AD. One of the important markers may be the concentration of UCHL1 and the proteasome in the blood serum. Their concentration can be affected by many factors, including eating habits. This study was conducted in 110 patients with early or moderate AD, with a mean age of 78.0 ± 8.1 years. The patients were under the care of the Podlasie Center of Psychogeriatrics and the Department of Neurology (Medical University of Białystok, Poland). The control group consisted of 60 healthy volunteers, matched for gender and age. The concentration of UCHL1 and the 20S proteasome subunit were measured by surface plasmon resonance imaging (SPRI). In addition, a nutritional interview was conducted with patients with AD, which assessed the frequency of consumption of 36 groups of products. In the group of patients with AD, compared to the control group, we showed a significantly higher concentration of UCHL1 (56.05 vs. 7.98 ng/mL) and the proteasome (13.02 vs. 5.72 µg/mL). Moreover, we found a low negative correlation between UCHL1 and the proteasome in the control group, and positive in the AD group. The analysis of eating habits showed that the consumption of selected groups of products may affect the concentration of the tested components, and therefore may have a protective effect on AD. Full article
(This article belongs to the Special Issue Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease)
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15 pages, 2376 KiB  
Article
The Clinical Significance of Cerebrospinal Fluid Reticulon 4 (RTN4) Levels in the Differential Diagnosis of Neurodegenerative Diseases
by Agnieszka Kulczyńska-Przybik, Maciej Dulewicz, Agnieszka Słowik, Renata Borawska, Alina Kułakowska, Jan Kochanowicz and Barbara Mroczko
J. Clin. Med. 2021, 10(22), 5281; https://doi.org/10.3390/jcm10225281 - 13 Nov 2021
Cited by 10 | Viewed by 2790
Abstract
Neurodegenerative diseases (NDs) belong to the top global causes of mortality. Diagnostic approaches to improve early diagnosis and differentiation of these diseases are constantly being sought. Therefore, we aimed to assess the cerebrospinal fluid (CSF) concentrations of Reticulon 4 (RTN4) in patients with [...] Read more.
Neurodegenerative diseases (NDs) belong to the top global causes of mortality. Diagnostic approaches to improve early diagnosis and differentiation of these diseases are constantly being sought. Therefore, we aimed to assess the cerebrospinal fluid (CSF) concentrations of Reticulon 4 (RTN4) in patients with neurodegenerative diseases and evaluate the potential clinical usefulness of this protein. RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. According to our best knowledge, this is the first investigation providing the data concerning the dynamic of CSF RTN4 protein levels in patients with different NDs. Methods: Overall, 77 newly diagnosed patients with neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), as well as 21 controls, were enrolled in the study. The CSF concentrations of tested proteins were assessed using immunological assays. Results: We revealed significantly higher CSF RTN4A levels in patients with AD, PD, and MS in comparison to the controls. Moreover, the comparative analysis of RTN4 concentration between different neurodegenerative diseases revealed the highest concentration of RTN4A in AD patients and a statistically significant difference between AD vs. PD, and AD vs. MS groups. The increased CSF level of the protein correlated with Tau, and pTau181 proteins in AD as well as in PD patients. Conclusions: Our study presents a previously not identified clinical utility of RTN4 in the differential diagnosis of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease)
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12 pages, 1454 KiB  
Article
Manual Correction of Voxel Misclassifications in Mesiotemporal Structures Does Not Alter Brain–Behavioral Results in an Episodic Memory Task
by Francina Hartmann, Julia Reinhardt, Christoph Stippich and Sabine Krumm
J. Clin. Med. 2021, 10(21), 4869; https://doi.org/10.3390/jcm10214869 - 22 Oct 2021
Cited by 1 | Viewed by 1589
Abstract
Voxel-based morphometry (VBM) is an established method for assessing grey matter volumes across the brain. The quality of magnetic resonance imaging (MRI) and the chosen data preprocessing steps can affect the outcome of VBM analyses. We recognized a lack of publicly available and [...] Read more.
Voxel-based morphometry (VBM) is an established method for assessing grey matter volumes across the brain. The quality of magnetic resonance imaging (MRI) and the chosen data preprocessing steps can affect the outcome of VBM analyses. We recognized a lack of publicly available and commonly used protocols, which indicates that standardized and optimized preprocessing protocols are needed. This paper focuses on the time- and resource-consuming manual correction of misclassifications of grey matter voxels in cortical structures important in Alzheimer’s dementia. A total of 126 individuals, including 63 patients with very early Alzheimer’s disease and 63 cognitively normal participants, received thorough neuropsychological testing and 3-Tesla MRI. Automated preprocessing of T1 MPRAGE images was performed, and misclassifications of grey matter voxels were manually identified and corrected. In a second run, the manual correction step was skipped. Multiple regression analyses using DARTEL in SPM8 were then conducted with the manually corrected and uncorrected sample, respectively. Manual correction of voxel misclassifications did not have a major impact on the correlation between episodic memory performance and structural brain imaging results. We conclude that, although performing all preprocessing steps remains the gold standard, skipping manual correction of voxel misclassifications is permitted when investigating populations on the Alzheimer’s disease spectrum. Full article
(This article belongs to the Special Issue Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease)
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13 pages, 973 KiB  
Article
Neurogranin and Neuronal Pentraxin Receptor as Synaptic Dysfunction Biomarkers in Alzheimer’s Disease
by Maciej Dulewicz, Agnieszka Kulczyńska-Przybik, Agnieszka Słowik, Renata Borawska and Barbara Mroczko
J. Clin. Med. 2021, 10(19), 4575; https://doi.org/10.3390/jcm10194575 - 2 Oct 2021
Cited by 11 | Viewed by 3120
Abstract
Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the [...] Read more.
Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer’s disease. Methods: Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology. Results: The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients. Conclusions: The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD. Full article
(This article belongs to the Special Issue Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease)
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12 pages, 1243 KiB  
Article
Association between Tooth Loss and Alzheimer’s Disease in a Nested Case–Control Study Based on a National Health Screening Cohort
by Ji Hee Kim, Jae Keun Oh, Jee Hye Wee, Yoo Hwan Kim, Soo-Hwan Byun and Hyo Geun Choi
J. Clin. Med. 2021, 10(17), 3763; https://doi.org/10.3390/jcm10173763 - 24 Aug 2021
Cited by 13 | Viewed by 2432
Abstract
Background: Reports on the possible risks for Alzheimer’s disease (AD) have included tooth loss as a potential risk factor. However, there are few studies addressing the association between tooth loss and AD in a large sample of participants. Accordingly, the objective of the [...] Read more.
Background: Reports on the possible risks for Alzheimer’s disease (AD) have included tooth loss as a potential risk factor. However, there are few studies addressing the association between tooth loss and AD in a large sample of participants. Accordingly, the objective of the current study was to explore the association of tooth loss with the development of AD in Korean adults. Methods: This nested case–control study, which is an analysis utilizing the data of the Korean National Health Insurance Service Health Screening Cohort study, randomly selected AD and control participants among Korean residents aged ≥60 years. The association between the number of missing teeth and AD occurrence was examined using a logistic regression model. Participants’ lifestyle factors (smoking and alcohol consumption) and various medical conditions and comorbidities were included as covariates. Results: The mean number of missing teeth was 2.94 in the AD group and 2.59 in the control group. After adjusting for covariates, tooth loss was significantly associated with AD, with an odds ratio (OR) (per 16 missing teeth) of 1.15 (95% confidence interval (CI) = 1.07–1.23, p < 0.001). Conclusions: Tooth loss remained consistently significantly associated with an increased risk of AD for both upper and lower tooth loss. A higher number of missing teeth was related to a higher probability of AD occurrence in an elderly Korean population. Efforts to manage tooth loss could be a possible approach to prevent AD. Full article
(This article belongs to the Special Issue Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease)
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14 pages, 1306 KiB  
Article
Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease
by Maciej Dulewicz, Agnieszka Kulczyńska-Przybik, Agnieszka Słowik, Renata Borawska and Barbara Mroczko
J. Clin. Med. 2021, 10(14), 3009; https://doi.org/10.3390/jcm10143009 - 6 Jul 2021
Cited by 12 | Viewed by 3697
Abstract
Background: Lipid metabolism-related biomarkers gain increasing researchers interest in the field of neurodegenerative disorders. Mounting evidence have indicated the role of fatty acid-binding proteins and pathology lipid metabolism in Alzheimer’s Disease (AD). The imbalance of fatty acids (FA) and lipids may negatively affect [...] Read more.
Background: Lipid metabolism-related biomarkers gain increasing researchers interest in the field of neurodegenerative disorders. Mounting evidence have indicated the role of fatty acid-binding proteins and pathology lipid metabolism in Alzheimer’s Disease (AD). The imbalance of fatty acids (FA) and lipids may negatively affect brain functions related to neurodegenerative disorders. The ApoE4 and FABP3 proteins may reflect processes leading to neurodegeneration. This study aimed to evaluate the relationship between the CSF levels of FABP3 and ApoE4 proteins and cognitive decline as well as the diagnostic performance of these candidate biomarkers in AD and mild cognitive impairment (MCI). Methods: A total of 70 subjects, including patients with AD, MCI, and non-demented controls, were enrolled in the study. CSF concentrations of FABP3 and ApoE4 were measured using immunoassay technology. Results: Significantly higher CSF concentrations of FABP3 and ApoE4 were observed in AD patients compared to MCI subjects and individuals without cognitive impairment. Both proteins were inversely associated with Aβ42/40 ratio: ApoE4 (rho = −0.472, p < 0.001), and FABP3 (rho = −0.488, p < 0.001) in the whole study group, respectively. Additionally, FABP3 was negatively correlated with Mini-Mental State Examination score in the whole study cohort (rho = −0.585 p < 0.001). Conclusion: Presented results indicate the pivotal role of FABP3 and ApoE4 in AD pathology as lipid-related biomarkers, but studies on larger cohorts are needed. Full article
(This article belongs to the Special Issue Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease)
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