Salivary alpha-synuclein in the diagnosis of Parkinson's disease and Progressive Supranuclear Palsy

Vivacqua, Giorgio; Suppa, Antonio; Mancinelli, Romina; Belvisi, Daniele; Fabbrini, A; Costanzo, Matteo; Formica, Alessandro; Onori, Paolo; Fabbrini, Giovanni

doi:10.1016/j.parkreldis.2019.02.014

Cited by 68 publications

(75 citation statements)

References 30 publications

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“…MiR-153 and miR-223 regulate α-synuclein, and several groups have shown increased levels of oligomeric α-synuclein and decreased levels of total α-synuclein in PD saliva. 12,16 In a randomly selected subset of the study population (22 PD patients and 30 controls), salivary oligomeric α-synuclein was increased, although not significantly, in PD saliva when compared with control preparations (P = 0.41). Although the ratio of oligomeric α-synuclein/miR-153 was significantly increased among PD patients (P < 0.05), this did not improve accuracy of the test ( Supplementary Fig.…”

Section: Ratiosmentioning

confidence: 99%

“…Saliva has advantages over other biofluids and imaging techniques because its acquisition is noninvasive, inexpensive, and requires minimal personnel training . Most groups report reduced salivary total α‐synuclein levels and higher oligomeric α‐synuclein levels in PD patients when compared with controls in addition to higher oligomeric to total α‐synuclein ratios …”

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confidence: 99%

“…10,11 Most groups report reduced salivary total α-synuclein levels and higher oligomeric α-synuclein levels in PD patients when compared with controls in addition to higher oligomeric to total α-synuclein ratios. [12][13][14][15][16] In 2018, we reported increased concentrations of salivary heme oxygenase-1 (HO-1) in early-stage PD patients when compared with non-neurological controls. 17 HO-1 catalyzes the degradation of heme to biliverdin (further catabolized to bilirubin), free ferrous iron, and carbon monoxide.…”

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confidence: 99%

“…Circulating levels of miR-153 and miR-223 were lower in the GFAP.HMOX1 mice when compared with age-matched, wild-type controls 30 commensurate with systemic alterations in the α-synuclein gene and protein expression profiles in idiopathic PD. 16,34,35 In the current study, we assessed salivary miR-153 and miR-223 levels as potential diagnostic biomarkers of PD relative to non-neurological controls.…”

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Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

et al. 2019

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Background Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of the world population older than 65 years of age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation of microRNAs (miRNAs) has been implicated in various neurodegenerative conditions, including PD. Distinct miRNAs have been demonstrated to be involved in the regulation of α‐synuclein, a key player in PD pathogenesis; miR‐153 and miR‐223 are downregulated in the brain and serum of parkinsonian GFAP.HMOX1 transgenic mice where they directly regulate α‐synuclein. Objective To ascertain whether salivary miR‐153 and miR‐223 are similarly downmodulated in, and may serve as diagnostic biomarkers of, idiopathic PD. Methods Using reverse transcriptase quantitative polymerase chain reaction, miR‐153 and miR‐223 levels were evaluated in the saliva of 77 non‐neurological controls and 83 PD patients. Levels of heme oxygenase‐1 and α‐synuclein were measured using enzyme‐linked immunosorbent assay. Analyses were adjusted by age, sex, medication exposure, disease duration, and relevant comorbidities. Results Log‐transformed expression levels of miR‐153 and miR‐223 were significantly decreased in the saliva of human PD patients in comparison with nonneurological controls. The miRNA expression levels did not change as a function of disease progression (Hoehn and Yahr staging). The area under the receiver operating characteristic curve separating controls from PD patients was 79% (95% confidence interval, 61%–96%) for miR‐153 and 77% (95% confidence interval, 59%–95%) for miR‐223. The ratios of miRNAs to oligomeric α‐synuclein, total α‐synuclein, or heme oxygenase‐1 protein did not improve accuracy of the test. Conclusion Salivary miR‐153 and miR‐223 levels may serve as useful, noninvasive, and relatively inexpensive diagnostic biomarkers of idiopathic PD. © 2019 International Parkinson and Movement Disorder Society

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confidence: 99%

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Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

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“…However, these differences did not reach statistical significance, suggesting that t‐a‐syn would not suffice as a single biomarker in saliva. Other studies have focused on evaluating o‐a‐syn, reporting a marked increase in PD patients compared to healthy controls (Kang et al 2016), suggesting that the oligomeric form may have a greater potential for a disease biomarker (Kang et al 2016; Vivacqua et al ; Vivacqua et al ). This was further supported when o‐α‐syn was evaluated in PD patients at different Hoehn & Yahr (H&Y) stages of the disease and reported significant increases with advancing disease stages.…”

Section: Levels Of Salivary α‐Synmentioning

confidence: 99%

Parkinson’s disease biomarkers based on α‐synuclein

Fayyad

Salim

Majbour

et al. 2019

Journal of Neurochemistry

109

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Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease and is estimated to affect approximately 1–4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease‐modifying therapies for Parkinson’s disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson’s disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non‐invasive means is a pressing issue in the field. Since the discovery of α‐synuclein (α‐syn) as a protein linked to a familial form of Parkinson’s disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson’s disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson’s disease biomarker discovery with a focus on α‐synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α‐synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions. “This article is part of the Special Issue Synuclein.”

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Salivary alpha‐synuclein as a potential fluid biomarker in Parkinson’s disease: A systematic review and meta‐analysis

et al. 2022

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Introduction Lewy bodies are the pathological hallmarks of Parkinson's disease. There is a need for effective biomarker that is cost effective, less invasive, and easily reproducible with good sensitivity and specificity and can be used to diagnose the condition early and track its severity and progression. Alpha‐synuclein (α‐syn), an integral component of the Lewy body, is found in saliva and can be a potential answer to the above concerns. Methods PubMed, EMBASE, Google Scholar, and CNKI databases, along with additional sites, were searched from January 2010 to August 2021. Standard mean difference (Hedges' g) with 95% CI was used to show an association. Statistical analysis was done using STATA software version 16 (StataCorp). Results We found a significant reduction in the mean difference of total salivary α‐syn among PD patients compared to healthy controls. However, the mean difference of oligomeric α‐syn and oligo/total salivary α‐syn ratio was significantly increased among PD patients compared to healthy controls. Conclusion Our systematic review and meta‐analysis found that salivary α‐syn parameters (total, oligomeric, oligo/total) can be considered a simple, easy‐to‐use, cost‐effective, and reliable diagnostic biomarker for PD and its progression.

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Salivary alpha-synuclein in the diagnosis of Parkinson's disease and Progressive Supranuclear Palsy

Cited by 68 publications

References 30 publications

Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

Parkinson’s disease biomarkers based on α‐synuclein

Salivary alpha‐synuclein as a potential fluid biomarker in Parkinson’s disease: A systematic review and meta‐analysis

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