Submit to Biomedicines Review for Biomedicines Propose a Special Issue

Journal Browser

Biomarkers for Parkinson’s Disease and Alzheimer’s Disease

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 16457

Share This Special Issue

Special Issue Editor

Dr. Ming-Jang Chiu

E-Mail Website
Guest Editor

1. Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 100, Taiwan
2. Department of Psychology, National Taiwan University, Taipei 106, Taiwan
Interests: neurodegenerative diseases; plasma biomarkers; neuroimaging; Alzheimer's disease; mild cognitive impairment; subjective cognitive decline; machine learning

Special Issue Information

Dear Colleagues,

Alzheimer's disease and Parkinson's disease are the two most common neurodegenerative diseases affecting more than several dozen million people worldwide. Recent advances in fluid and neuroimage biomarkers help to characterize pathophysiological signatures of these neurodegenerative diseases.

New molecular ligands targeting the deposition of pathological proteins, such as amyloid or tau (positron emission tomography) PET scans, are already used in enrolling participants and monitoring therapeutic responses of clinical trials. Novel techniques can measure proteins of Pico- or even Femto- g/ml level in cerebrospinal fluid (CSF) and blood (e.g., amyloid, tau, alpha-synuclein species, and neurofilaments), making their application more convenient. Susceptibility-weighted images for nigrasome-1 help to delineate the severity of Parkinson's disease. Submillimeter MRI for segmentation of subcortical brain regions or hippocampal subfields sheds light on the prodromal/preclinical diagnosis of neurodegenerative diseases.

In this Special Issue of Biomedicines, we would like to solicit original research papers focusing on cutting-edge techniques and their clinical applications, including but not limited to fluid biomarkers (blood and CSF) and molecular imaging (PET or MRI). Research exploring different species of pathological proteins, i.e., their phosphorylated, oligomeric, or isomeric derivatives, are all welcomed. Review articles can be arranged through discussion with the section editor.

Dr. Ming-Jang Chiu
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

Biomarker
Alzheimer's disease
Parkinson's disease

Published Papers (6 papers)

Download All Papers

Research

Jump to: Other

13 pages, 1294 KiB

Open AccessArticle

Cerebrospinal Fluid Neurofilament Light Predicts Risk of Dementia Onset in Cognitively Healthy Individuals and Rate of Cognitive Decline in Mild Cognitive Impairment: A Prospective Longitudinal Study

by Kunal Dhiman, Victor L. Villemagne, Christopher Fowler, Pierrick Bourgeat, Qiao-Xin Li, Steven Collins, Ashley I. Bush, Christopher C. Rowe, Colin L. Masters, David Ames, Kaj Blennow, Henrik Zetterberg, Ralph N. Martins and Veer Gupta

Biomedicines 2022, 10(5), 1045; https://doi.org/10.3390/biomedicines10051045 - 30 Apr 2022

Cited by 2 | Viewed by 2378

Abstract

Background: Biomarkers that are indicative of early biochemical aberrations are needed to predict the risk of dementia onset and progression in Alzheimer’s disease (AD). We assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) chain for screening preclinical AD, predicting dementia onset among cognitively healthy (CH) individuals, and the rate of cognitive decline amongst individuals with mild cognitive impairment (MCI). Methods: Neurofilament light levels were measured in CSF samples of participants (CH, n = 154 and MCI, n = 32) from the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL). Cases of preclinical AD were identified using biomarker-guided classification (CH, amyloid-β [Aβ]+, phosphorylated-tau [P-tau]+ and total-tau [T-tau]±; A+T+/N±). The prediction of dementia onset (questionable dementia) among CH participants was assessed as the risk of conversion from Clinical Dementia Rating [CDR = 0] to CDR ≥ 0.5 over 6 years. Mixed linear models were used to assess the utility of baseline CSF NfL levels for predicting the rate of cognitive decline among participants with MCI over 4.5 years. Results: Neurofilament light levels were significantly higher in preclinical AD participants (CH, A+T+/N±) as compared to A-T-N- (p < 0.001). Baseline levels of CSF NfL were higher in CH participants who converted to CDR ≥ 0.5 over 6 years (p = 0.045) and the risk of conversion to CDR ≥ 0.5 was predicted (hazard ratio [HR] 1.60, CI 1.03–2.48, p = 0.038). CH participants with CSF NfL > cut-off were at a higher risk of developing dementia (HR 4.77, CI 1.31–17.29, p = 0.018). Participants with MCI and with higher baseline levels of CSF NfL (>median) had a higher rate of decline in cognition over 4.5 years. Conclusion: An assessment of CSF NfL levels can help to predict dementia onset among CH vulnerable individuals and cognitive decline among those with MCI. Full article

(This article belongs to the Special Issue Biomarkers for Parkinson’s Disease and Alzheimer’s Disease)

► Show Figures

Figure 1

15 pages, 1859 KiB

Open AccessArticle

Mitochondrial Genetics Reinforces Multiple Layers of Interaction in Alzheimer’s Disease

by Giovanna Chaves Cavalcante, Leonardo Miranda Brito, Ana Paula Schaan, Ândrea Ribeiro-dos-Santos, Gilderlanio Santana de Araújo and on behalf of Alzheimer’s Disease Neuroimaging Initiative

Biomedicines 2022, 10(4), 880; https://doi.org/10.3390/biomedicines10040880 - 12 Apr 2022

Cited by 8 | Viewed by 2797

Abstract

Nuclear DNA has been the main source of genome-wide loci association in neurodegenerative diseases, only partially accounting for the heritability of Alzheimer’s Disease (AD). In this context, mitochondrial DNA (mtDNA) is gaining more attention. Here, we investigated mitochondrial genes and genetic variants that may influence mild cognitive impairment and AD, through an integrative analysis including differential gene expression and mitochondrial genome-wide epistasis. We assessed the expression of mitochondrial genes in different brain tissues from two public RNA-Seq databases (GEO and GTEx). Then, we analyzed mtDNA from the ADNI Cohort and investigated epistasis regarding mitochondrial variants and levels of A

β_{1 - 42}

, TAU, and Phosphorylated TAU (PTAU) from cognitively healthy controls, and both mild cognitive impairment (MCI) and AD cases. We identified multiple differentially expressed mitochondrial genes in the comparisons between cognitively healthy individuals and AD patients. We also found increased protein levels in MCI and AD patients when compared to healthy controls, as well as novel candidate networks of mtDNA epistasis, which included variants in all mitochondrially-encoded oxidative phosphorylation complexes, 12S rRNA and MT-DLOOP. Our results highlight layers of potential interactions involving mitochondrial genetics and suggest specific molecular alterations as potential biomarkers for AD. Full article

(This article belongs to the Special Issue Biomarkers for Parkinson’s Disease and Alzheimer’s Disease)

► Show Figures

Figure 1

11 pages, 4302 KiB

Open AccessArticle

Differential Transcriptome Profiling Unveils Novel Deregulated Gene Signatures Involved in Pathogenesis of Alzheimer’s Disease

by Himanshu Narayan Singh, Vishnu Swarup, Navneet Kumar Dubey, Niraj Kumar Jha, Anjani Kumar Singh, Wen-Cheng Lo and Sanjay Kumar

Biomedicines 2022, 10(3), 611; https://doi.org/10.3390/biomedicines10030611 - 6 Mar 2022

Cited by 2 | Viewed by 2744

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a progressive loss of cognitive functions at a higher level than normal aging. Although the apolipoprotein (APOE) gene is a major risk factor in developing AD, other genes have also been reported to be linked with complex phenotypes. Therefore, this genome-wide expression study explored differentially expressed genes as possible novel biomarkers involved in AD. The mRNA expression dataset, GSE28146, containing 15 sample data composed of 7 AD cases from the hippocampus region with age-matched control (n = 8, >80 years), was analyzed. Using “affy” R-package, mRNA expression was calculated, while pathway enrichment analysis was performed to determine related biological processes. Of 58 differentially expressed genes, 44 downregulated and 14 upregulated genes were found to be significantly (p < 0.001) altered. The pathway enrichment analysis revealed two altered genes, i.e., dynein light chain 1 (DYNLL1) and kalirin (KLRN), associated with AD in the elderly population. The majority of genes were associated with retrograde endocannabinoid as well as vascular endothelial growth factors affecting the complex phenotypes. The DYNLL1 and KLRN genes may be involved with AD and Huntington’s disease (HD) phenotypes and represent a common genetic basis of these diseases. However, the hallmark of AD is dementia, while the classic motor sign of HD includes chorea. Our data warrant further investigation to identify the role of these genes in disease pathogenesis. Full article

(This article belongs to the Special Issue Biomarkers for Parkinson’s Disease and Alzheimer’s Disease)

► Show Figures

Figure 1

15 pages, 1135 KiB

Open AccessArticle

Qualitative and Quantitative Comparison of Hippocampal Volumetric Software Applications: Do All Roads Lead to Rome?

by Stephanie Mangesius, Lukas Haider, Lukas Lenhart, Ruth Steiger, Ferran Prados Carrasco, Christoph Scherfler and Elke R. Gizewski

Biomedicines 2022, 10(2), 432; https://doi.org/10.3390/biomedicines10020432 - 12 Feb 2022

Viewed by 2684

Abstract

Brain volumetric software is increasingly suggested for clinical routine. The present study quantifies the agreement across different software applications. Ten cases with and ten gender- and age-adjusted healthy controls without hippocampal atrophy (median age: 70; 25–75% range: 64–77 years and 74; 66–78 years) were retrospectively selected from a previously published cohort of Alzheimer’s dementia patients and normal ageing controls. Hippocampal volumes were computed based on 3 Tesla T1-MPRAGE-sequences with FreeSurfer (FS), Statistical-Parametric-Mapping (SPM; Neuromorphometrics and Hammers atlases), Geodesic-Information-Flows (GIF), Similarity-and-Truth-Estimation-for-Propagated-Segmentations (STEPS), and Quantib™. MTA (medial temporal lobe atrophy) scores were manually rated. Volumetric measures of each individual were compared against the mean of all applications with intraclass correlation coefficients (ICC) and Bland–Altman plots. Comparing against the mean of all methods, moderate to low agreement was present considering categorization of hippocampal volumes into quartiles. ICCs ranged noticeably between applications (left hippocampus (LH): from 0.42 (STEPS) to 0.88 (FS); right hippocampus (RH): from 0.36 (Quantib™) to 0.86 (FS). Mean differences between individual methods and the mean of all methods [mm³] were considerable (LH: FS −209, SPM-Neuromorphometrics −820; SPM-Hammers −1474; Quantib™ −680; GIF 891; STEPS 2218; RH: FS −232, SPM-Neuromorphometrics −745; SPM-Hammers −1547; Quantib™ −723; GIF 982; STEPS 2188). In this clinically relevant sample size with large spread in data ranging from normal aging to severe atrophy, hippocampal volumes derived by well-accepted applications were quantitatively different. Thus, interchangeable use is not recommended. Full article

(This article belongs to the Special Issue Biomarkers for Parkinson’s Disease and Alzheimer’s Disease)

► Show Figures

Graphical abstract

Other

Jump to: Research

16 pages, 711 KiB

Open AccessSystematic Review

Microbiota Dysbiosis in Parkinson Disease—In Search of a Biomarker

by Julia Maya Nowak, Mateusz Kopczyński, Andrzej Friedman, Dariusz Koziorowski and Monika Figura

Biomedicines 2022, 10(9), 2057; https://doi.org/10.3390/biomedicines10092057 - 23 Aug 2022

Cited by 9 | Viewed by 2775

Abstract

Numerous studies have highlighted the role of the gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced by specific gut bacteria. This review’s aim is to identify gut bacterial biomarkers of Parkinson disease. A comprehensive search for original research papers on gut microbiota composition in Parkinson disease was conducted using the PubMed, Embase, and Scopus databases. Research papers on intestinal permeability, nasal and oral microbiomes, and interventional studies were excluded. The yielded results were categorized into four groups: Parkinson disease vs. healthy controls; disease severity; non-motor symptoms; and clinical phenotypes. This review was conducted in accordance with the PRISMA 2020 statement. A total of 51 studies met the eligibility criteria. In the Parkinson disease vs. healthy controls group, 22 bacteria were deemed potentially important. In the disease severity category, two bacteria were distinguished. In the non-motor symptoms and clinical phenotypes categories, no distinct pathogen was identified. The studies in this review report bacteria of varying taxonomic levels, which prevents the authors from reaching a clear conclusion. Future research should follow a unified methodology in order to identify potential biomarkers for Parkinson disease. Full article

(This article belongs to the Special Issue Biomarkers for Parkinson’s Disease and Alzheimer’s Disease)

► Show Figures

Figure 1

25 pages, 948 KiB

Open AccessSystematic Review

Systematic Review on Saliva Biomarkers in Patients Diagnosed with Morbus Alzheimer and Morbus Parkinson

by Michael Wolgin, Magdalena Zobernig, Valentyn Dvornyk, Ralf J. Braun and Andrej M. Kielbassa

Biomedicines 2022, 10(7), 1702; https://doi.org/10.3390/biomedicines10071702 - 14 Jul 2022

Cited by 11 | Viewed by 2160

Abstract

Extracellular plaques composed of the hydrophobic peptide amyloid-β and intraneuronal accumulation of the hyperphosphorylated protein tau (p-tau) are pathological hallmarks found in the brains of most people affected by Alzheimer’s disease (AD). In Parkinson’s disease (PD), Lewy bodies, i.e., intraneuronal protein deposits comprising the protein α-synuclein, are a typical disease feature. As these hallmarks located in the brain are hardly traceable, reliable biomarkers from easily accessible body fluids are key for accurate diagnosis. The aim of the present work was to review the available literature regarding potential biomarkers of AD and PD in the saliva. The databases PubMed, Google Scholar, LILACS, LIVIVO, VHL regional portal, Cochrane Library, eLIBRARY, and IOS Press were consulted for the literature search. Screening of titles and abstracts followed the PRISMA guidelines, while data extraction and the assessment of full texts were carried out in accordance with the Newcastle–Ottawa Scale assessment. The review shows significant increases in levels of the amyloid-β Aβ1-42 and elevated p-tau to total tau (t-tau) ratios in salivary samples of AD patients, in comparison with healthy controls. In PD patients, levels of α-synuclein in salivary samples significantly decreased compared to healthy controls, whereas oligomeric α-synuclein and the ratio of oligomeric α-synuclein to total α-synuclein markedly increased. Salivary biomarkers represent a promising diagnostic tool for neurodegenerative diseases. Further high-quality case–control studies are needed to substantiate their accuracy. Full article

(This article belongs to the Special Issue Biomarkers for Parkinson’s Disease and Alzheimer’s Disease)

► Show Figures