Recent Developments in Circulating Biomarkers in Parkinson’s Disease: The Potential Use of Mirnas in A Clinical Setting

Santos, Márcia Cristina Teixeira dos; Bell, Rosie; Costa, André Nogueira da

doi:10.4155/bio-2016-0166

Cited by 17 publications

(10 citation statements)

References 178 publications

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“…Several studies have highlighted altered levels of α-synuclein (α-syn), DJ-1, amyloid beta (Aβ) and Tau proteins in late stage, symptomatically identified PD patients compared with controls [ 12 – 17 ]. Nevertheless, these findings are not consistently observed in different studies [ 18 ].…”

Section: Introductionmentioning

confidence: 80%

Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis

Santos

Scheller²,

Schulte

et al. 2018

PLoS ONE

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Cerebrospinal fluid (CSF) has often been used as the source of choice for biomarker discovery with the goal to support the diagnosis of neurodegenerative diseases. For this study, we selected 15 CSF protein markers which were identified in previously published clinical investigations and proposed as potential biomarkers for PD diagnosis. We aimed at investigating and confirming their suitability for early stage diagnosis of the disease. The current study was performed in a two-fold confirmatory approach. Firstly, the CSF protein markers were analysed in confirmatory cohort I comprising 80 controls and 80 early clinical PD patients. Through univariate analysis we found significant changes of six potential biomarkers (α-syn, DJ-1, Aβ42, S100β, p-Tau and t-Tau). In order to increase robustness of the observations for potential patient differentiation, we developed–based on a machine learning approach—an algorithm which enabled identifying a panel of markers which would improve clinical diagnosis. Based on that model, a panel comprised of α-syn, S100β and UCHL1 were suggested as promising candidates. Secondly, we aimed at replicating our observations in an independent cohort (confirmatory cohort II) comprising 30 controls and 30 PD patients. The univariate analysis demonstrated Aβ42 as the only reproducible potential biomarker. Taking into account both technical and clinical aspects, these observations suggest that the large majority of the investigated CSF proteins currently proposed as potential biomarkers lack robustness and reproducibility in supporting diagnosis in the early clinical stages of PD.

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Section: Introductionmentioning

confidence: 80%

Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis

Santos

Scheller²,

Schulte

et al. 2018

PLoS ONE

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“…In our study, we analyzed total α-syn in the CSF and found it expressed in lower levels in the CSF of early stage PD patients compared to controls. Although the majority of publications support this finding, there is still conflicting data available [ 15 ]. Furthermore, different isoforms of α-syn have been investigated and proposed as potential biomarkers, including monomeric and phosphorylated forms, among others [ 9 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, studies have highlighted altered levels of α-syn and DJ-1 in PD patients compared with controls [ 9 – 14 ]. Furthermore, due to assay incompatibility and lack of standardized protocols, results are conflicting and do not show robustness for use as clinical biomarkers [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Due to their ability to cross the Blood Brain Barrier (BBB) and being both free in circulation as well as present in exosomes, miRNAs have the potential to be valuable biomarkers providing insights to the pathological signs detected in the Central Nervous System (CNS) [ 21 ]. miRNAs have been used as biomarkers for a potential non-invasive diagnosis of several disorders [ 22 – 25 ], but only a limited number of miRNAs have been implicated with PD [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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miRNA-based signatures in cerebrospinal fluid as potential diagnostic tools for early stage Parkinson’s disease

et al. 2018

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Parkinson’s Disease is the second most common neurodegenerative disorder, affecting 1–2% of the elderly population. Its diagnosis is still based on the identification of motor symptoms when a considerable number of dopaminergic neurons are already lost. The development of translatable biomarkers for accurate diagnosis at the earliest stages of PD is of extreme interest. Several microRNAs have been associated with PD pathophysiology. Consequently, microRNAs are emerging as potential biomarkers, especially due to their presence in Cerebrospinal Fluid and peripheral circulation. This study employed small RNA sequencing, protein binding ligand assays and machine learning in a cross-sectional cohort comprising 40 early stage PD patients and 40 well-matched controls. We identified a panel comprising 5 microRNAs (Let-7f-5p, miR-27a-3p, miR-125a-5p, miR-151a-3p and miR-423-5p), with 90% sensitivity, 80% specificity and 82% area under the curve (AUC) for the differentiation of the cohorts. Moreover, we combined miRNA profiles with hallmark-proteins of PD and identified a panel (miR-10b-5p, miR-22-3p, miR-151a-3p and α-synuclein) reaching 97% sensitivity, 90% specificity and 96% AUC. We performed a gene ontology analysis for the genes targeted by the microRNAs present in each panel and showed the likely association of the models with pathways involved in PD pathogenesis.

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“…The microRNA regulatory network in PD has been discussed before, particularly in the potential of miRNAs as circulating biomarkers for the diagnosis and treatment of PD (dos Santos et al, 2016 ; Ma et al, 2016 ; Marques et al, 2016 ; Mushtaq et al, 2016 ; Batistela et al, 2017 ), in PD progression (Heman-Ackah et al, 2013 ) as well as in the oxidative stress pathway (Qiu et al, 2014 ; Xie and Chen, 2016 ). However, none of these discussions emphasis on the potential of these miRNAs to differentiate the EOPD from LOPD.…”

Section: Microrna Regulatory Network In Parkinson Diseasementioning

confidence: 99%

MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

Arshad

Sulaiman

Saperi

et al. 2017

Front. Mol. Neurosci.

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Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis.

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Recent Developments in Circulating Biomarkers in Parkinson’s Disease: The Potential Use of Mirnas in A Clinical Setting

Cited by 17 publications

References 178 publications

Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis

Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson’s disease diagnosis

miRNA-based signatures in cerebrospinal fluid as potential diagnostic tools for early stage Parkinson’s disease

MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

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