Combining Skin α‐Synuclein <scp>Real‐Time Quaking‐Induced Conversion</scp> and Circulating Neurofilament Light Chain to Distinguish Multiple System Atrophy and Parkinson's Disease

Martínez-Valbuena, Iván; Visanji, Naomi P.; Olszewska, Diana A.; Sousa, Mário; Bhakta, Puja; Vasilevskaya, Anna; Anastassiadis, Chloe; Tartaglia, Maria Carmela; Kovács, Gábor G.; Lang, Anthony E.

doi:10.1002/mds.28912

Cited by 20 publications

(13 citation statements)

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“…The detected biofluids and peripheral tissues included CSF, skin, OM, saliva, GI tract, and NEs from plasma, serum and SMG. The characteristics of these studies are described in Table 1 [7–14, 16–49, 65]. The PRISMA flowchart is displayed in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Comparison of biospecimens for α‐synuclein seed amplification assays in Parkinson's disease: A systematic review and network meta‐analysis

Zheng

Yang

et al. 2023

Euro J of Neurology

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BackgroundAlpha‐synuclein seed amplification assays (α‐syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α‐syn SAAs on biofluids and peripheral tissues.MethodsA comprehensive research was performed on PubMed, Web of Science, Embase, and Cochrane library. Meta‐analysis was performed using a random‐effects model. A Network meta‐analysis (NMA) based on ANOVA model was conducted to compare the relative accuracy of α‐syn SAAs on different specimens.ResultsThe pooled sensitivity and specificity of α‐syn SAAs distinguishing PD from HCs or NNCs were 0.91 (0.86‐0.94) and 0.92 (0.87‐0.95) for cerebrospinal fluid (CSF); 0.91 (0.87‐0.96) and 0.93 (0.88‐0.97) for skin; 0.44 (0.30‐0.59) and 0.92 (0.79‐0.98) for submandibular gland; 0.44 (0.30‐0.59) and 0.92 (0.79‐0.98) for gastrointestinal tract; 0.79 (0.70‐0.86) and 0.88 (0.77‐0.95) for saliva; 0.52 (0.38‐0.66) and 0.91 (0.82‐0.97) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (0.89‐0.93) and 0.50 (0.45‐0.56) for CSF, 0.92 (0.83‐0.97) and 0.22 (0.06‐0.48) for skin, 0.61 (0.42‐0.78) and 0.49 (0.33‐0.65) for OM in distinguishing PD from MSA. The pooled sensitivity and specificity were 0.92 (0.89‐0.94) and 0.84 (0.73‐0.91) for CSF, 0.92 (0.83‐0.97) and 0.88 (0.64‐0.99) for skin, 0.69 (0.56‐0.80) and 0.83 (0.59‐0.96) for OM in distinguishing PD from PSP. The pooled sensitivity and specificity were 0.94 (0.90‐0.97) and 0.95 (0.77‐1.00) for CSF, 0.94 (0.84‐0.99) and 0.86 (0.42‐1.00) for skin in distinguishing PD from CBD.Conclusionsα‐syn SAAs of CSF, skin, saliva, SMG and OM are promising diagnostic assays for PD, with CSF and skin α‐syn SAAs demonstrating higher diagnostic performance.

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Section: Resultsmentioning

confidence: 99%

Comparison of biospecimens for α‐synuclein seed amplification assays in Parkinson's disease: A systematic review and network meta‐analysis

Zheng

Yang

et al. 2023

Euro J of Neurology

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“…A total of 132 patients have been screened in 27 months, and about a hundred have been enrolled with various clinical presentations fulfilling MDS criteria of possible or probable PSP, and over 50% have already completed a first follow-up visit despite the intervening COVID pandemic. It is important to note that during this time, several research initiatives derived from this cohort have been conducted including epidemiological study of the cohort, the development of reliable diagnostic biomarkers, 15 testing and validation of current diagnostic criteria, evaluation of a virtual version of the PSP Rating Scale, 16 and the description of a “protracted course PSP.” 13 An evaluation of the response to pharmacologic and non-pharmacologic treatments is under preparation for peer-reviewed publication.…”

Section: Discussionmentioning

confidence: 99%

The Rossy Progressive Supranuclear Palsy Centre: Creation and Initial Experience

Couto

Fox

Tartaglia

et al. 2023

Can. J. Neurol. Sci.

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Objective: To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The Rossy PSP Centre, to share the data acquisition tools adopted, and to report preliminary results. Methods: Extensive demographic and longitudinal clinical information is collected every 6 months using standardized forms. Biofluids are collected for biobanking and genetic analysis, and many patients are enrolled in neuroimaging research protocols. Brain donation is an important component of the program, and standardized processing protocols have been established, including very short death to autopsy times in patients undergoing medical assistance in dying. Results: Between Oct 2019 and Dec 2021, 132 patients were screened, 91 fulfilling criteria for PSP and 19 for CBS; age 71 years; 41% female; duration 5 years, age-of-onset 66 years. The most common symptoms at onset were postural instability and falls (45%), cognitive-behavioral changes (22%), and Parkinsonism (9%). The predominant clinical phenotype was Richardson syndrome (82%). Levodopa and amantadine resulted in partial and short-lasting benefit. Conclusions: The Rossy PSP Centre has been established to advance clinical and basic research in PSP and related tauopathies. The extent of the clinical data collected permits deep phenotyping of patients and allows for future clinical and basic research. Preliminary results showed expected distribution of phenotypes, demographics, and response to symptomatic treatments in our cohort. Longitudinal data will provide insight into the early diagnosis and management of PSP. Future steps include enrollment of patients in earlier stages, development of biomarkers, and fast-tracking well-characterized patients into clinical trials.

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“…Deposits of either α-synuclein or phosphorylated α-synuclein were found in CSF, however, a meta-analysis did not confirm a significant difference in total α-synuclein between patients with PD and other synucleinopathies or APS (17). The combinations of either total α-synuclein with NFL (18) or total α-synuclein with amyloid beta 1-42 peptide and NFL (19) could be promising approach for the differential diagnosis of PD and APSs.…”

Section: Alpha-synucleinmentioning

confidence: 92%

Search for Molecular Biomarkers of Parkinson’s Disease. New Tissues and Methods

Račay¹

2023

Acta Medica Martiniana

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Parkinson’s disease (PD) is a chronic neurodegenerative disorder that is clinically manifested by motor and non-motor symptoms. At the early stage of the disease, it can be misdiagnosed with some neurologic disorders due to overlapping or similar clinical features. In addition, the pathogenesis of this disease is initiated several years prior to the appearance of classical motor symptoms. This latent phase of neurodegeneration in PD characterised at cellular level by preservation of significant fraction of dopaminergic neurones is of particular interest with respect to the development of disease-modifying or neuroprotective therapies which would require intervention at the earliest stages of disease with an aim to slow down or reverse the disease progression. Therefore, huge effort was performed in order to find and validate a biomarker that would reliably differentiate PD from other neurologic diseases as well as a biomarker that would reveal preclinical/prodromal stage of PD. This short review summarises a recent progress in validation of molecular biomarkers of PD, distinct from genetic markers of PD, with some focus on new analysed tissues and new methods.

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Combining Skin α‐Synuclein Real‐Time Quaking‐Induced Conversion and Circulating Neurofilament Light Chain to Distinguish Multiple System Atrophy and Parkinson's Disease

Cited by 20 publications

References 8 publications

Comparison of biospecimens for α‐synuclein seed amplification assays in Parkinson's disease: A systematic review and network meta‐analysis

Comparison of biospecimens for α‐synuclein seed amplification assays in Parkinson's disease: A systematic review and network meta‐analysis

The Rossy Progressive Supranuclear Palsy Centre: Creation and Initial Experience

Search for Molecular Biomarkers of Parkinson’s Disease. New Tissues and Methods

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