Evidence map›Paper›PMID 35655068›Full record

ArticleNPJ Parkinson's disease2022

Quantitative detection of α-Synuclein and Tau oligomers and other aggregates by digital single particle counting.

Lara Blömeke, Marlene Pils, Victoria Kraemer-Schulien, Alexandra Dybala, Anja Schaffrath, Andreas Kulawik, Fabian Rehn, Anneliese Cousin, Volker Nischwitz, Johannes Willbold and 12 more

Abstract read
In one paragraph

Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 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

22 authors.

Lara BlömekeInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.ORCID http://orcid.org/0000-0002-8861-9224
Marlene Pilsattyloid GmbH, 40225, Düsseldorf, Germany.
Victoria Kraemer-SchulienInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Alexandra Dybalaattyloid GmbH, 40225, Düsseldorf, Germany.
Anja SchaffrathInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.ORCID http://orcid.org/0000-0002-3084-3557
Andreas KulawikInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Fabian RehnInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.ORCID http://orcid.org/0000-0001-8815-0684
Anneliese CousinInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Volker NischwitzCentral Institute for Engineering, Electronics and Analytics, Analytics (ZEA-3), Forschungszentrum Jülich, 52428, Jülich, Germany.ORCID http://orcid.org/0000-0002-9261-3124
Johannes WillboldInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Rebecca ZackDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Thomas F TropeaDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Tuyen BujnickiInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Gültekin TamgüneyInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Daniel WeintraubCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
David IrwinDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Murray GrossmanDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
John Q TrojanowskiCenter for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Oliver BannachInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.
Alice Chen-PlotkinDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dieter WillboldInstitute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany. d.willbold@fz-juelich.de.ORCID http://orcid.org/0000-0002-0065-7366

Funding

Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
NIA NIH HHS P30 AG072979
6 · The paper itself

Abstract

The pathological hallmark of neurodegenerative diseases is the formation of toxic oligomers by proteins such as alpha-synuclein (aSyn) or microtubule-associated protein tau (Tau). Consequently, such oligomers are promising biomarker candidates for diagnostics as well as drug development. However, measuring oligomers and other aggregates in human biofluids is still challenging as extreme sensitivity and specificity are required. We previously developed surface-based fluorescence intensity distribution analysis (sFIDA) featuring single-particle sensitivity and absolute specificity for aggregates. In this work, we measured aSyn and Tau aggregate concentrations of 237 cerebrospinal fluid (CSF) samples from five cohorts: Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and a neurologically-normal control group. aSyn aggregate concentration discriminates PD and DLB patients from normal controls (sensitivity 73%, specificity 65%, area under the receiver operating curve (AUC) 0.68). Tau aggregates were significantly elevated in PSP patients compared to all other groups (sensitivity 87%, specificity 70%, AUC 0.76). Further, we found a tight correlation between aSyn and Tau aggregate titers among all patient cohorts (Pearson coefficient of correlation r = 0.81). Our results demonstrate that aSyn and Tau aggregate concentrations measured by sFIDA differentiate neurodegenerative disease diagnostic groups. Moreover, sFIDA-based Tau aggregate measurements might be particularly useful in distinguishing PSP from other parkinsonisms. Finally, our findings suggest that sFIDA can improve pre-clinical and clinical studies by identifying those individuals that will most likely respond to compounds designed to eliminate specific oligomers or to prevent their formation.

Identifiers

PMID35655068
PMCPMC9163356

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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.