Evidence map›Paper›PMID 36096686›Full record

ArticleNeurology2022

Disease-Associated α-Synuclein Aggregates as Biomarkers of Parkinson Disease Clinical Stage.

Nour Majbour, Jan Aasly, Ilham Abdi, Simona Ghanem, Daniel Erskine, Wilma van de Berg, Omar El-Agnaf

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In one paragraph

Article in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Nour MajbourFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands.ORCID 0000-0002-7544-8497
Jan AaslyFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands.
Ilham AbdiFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands.
Simona GhanemFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands.
Daniel ErskineFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands.
Wilma van de BergFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands.ORCID 0000-0002-6175-5357
Omar El-AgnafFrom the Neurological Disorders Research Centre (N.M., I.A., S.G., O.E.-A.), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha; MRC Prion Unit at University College London (UCL) (N.M.), UCL Institute of Prion Diseases, UCL, United Kingdom; Department of Neuroscience (J.A.), Norwegian University of Science and Technology, (NTNU), Trondheim; Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway; Translational and Clinical Research Institute (D.E.), Newcastle University, United Kingdom; and Amsterdam UMC (W.B.), location VUmc, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience, the Netherlands. oelagnaf@hbku.edu.qa.ORCID 0000-0002-6850-8084

Funding

Medical Research Council
6 · The paper itself

Abstract

BACKGROUND AND

objectivesRobust biomarkers that can mirror Parkinson disease (PD) are of great significance. In this study, we present a novel approach to investigate disease-associated α-synuclein (αSyn) aggregates as biomarkers of PD clinical stage.

methodsWe combined both seed amplification assay (SAA) and ELISA to provide a quantitative test readout that reflects the clinical severity of patients with PD. To attain this goal, we initially explored the potential of our test using 2 sets of human brain homogenates (pilot and validation sets) and then verified it with 2 independent human CSF cohorts; discovery (62 patients with PD and 34 controls) and validation (49 patients with PD and 48 controls) cohorts.

resultsWe showed that oligomers-specific ELISA robustly quantified SAA end product from patients with PD or dementia with Lewy bodies with high sensitivity and specificity scores (100%). Analysis also demonstrated that seeding activity could be detected earlier with oligomeric ELISA as the test readout rather than SAA alone. Of more importance, multiplexing the assays provided robust information about the patients' clinical disease stage. In the discovery cohort, levels of CSF-seeded αSyn oligomers correlated with the severity of the clinical symptoms of PD as measured by the Unified Parkinson Disease Rating Scale (UPDRS) motor ( DISCUSSION: We showed that combining SAA and ELISA assays is a more promising diagnostic tool than SAA alone, providing information about the disease stage by correlating with clinical measures of disease severity. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CSF-seeded αSyn oligomers can accurately discriminate patients with PD and normal controls and CSF-seeded αSyn oligomers levels correlate with PD severity.

Indexed as

alpha-SynucleinParkinson DiseaseBiomarkersBrainHumansROC Curvealpha-SynucleinBiomarkers

Identifiers

PMID36096686
PMCPMC9687407

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.