ArticleNeuropathology and applied neurobiology2017
Novel conformation-selective alpha-synuclein antibodies raised against different in vitro fibril forms show distinct patterns of Lewy pathology in Parkinson's disease.
Article in Neuropathology and applied neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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.
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.
Who cites it
45 citing papers in PubMed, 63 citations in OpenAlex.
- A novel hierarchical framework elucidating regional differences in α-synuclein and tau co-pathology in military veterans with parkinsonism.Journal of neuropathology and experimental neurology · 2026Article
- Blood α-Synuclein Separates Parkinson's Disease from Dementia with Lewy Bodies.Annals of neurology · 2025Article
- Novel in situ seeding immunodetection assay uncovers neuronal-driven alpha-synuclein seeding in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- α-Synuclein Pathology in Synucleinopathies: Mechanisms, Biomarkers, and Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Facile generation of drug-like conformational antibodies specific for amyloid fibrils.Nature chemical biology · 2025Article
- Alterations of diffusion kurtosis measures in gait-related white matter in the "ON-OFF state" of Parkinson's disease.Chinese medical journal · 2025Article
- N-terminus α-synuclein detection reveals new and more diverse aggregate morphologies in multiple system atrophy and Parkinson's disease.Translational neurodegeneration · 2024Article
- Review
- α-Synuclein Conformations in Plasma Distinguish Parkinson's Disease from Dementia with Lewy Bodies.Research square · 2024Article
- Toward the quantification of α-synuclein aggregates with digital seed amplification assays.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases.NPJ Parkinson's disease · 2023Article
- Identification of a Putative α-synuclein Radioligand Using an in silico Similarity Search.Molecular imaging and biology · 2023Article
- Artificial intelligence-coupled plasmonic infrared sensor for detection of structural protein biomarkers in neurodegenerative diseases.Science advances · 2023Article
- Article
- Oligodendrocytes Prune Axons Containing α-Synuclein Aggregates In Vivo: Lewy Neurites as Precursors of Glial Cytoplasmic Inclusions in Multiple System Atrophy?Biomolecules · 2023Article
- Monitoring α-synuclein aggregation.Neurobiology of disease · 2023Review
- α-Synuclein Seed Amplification in CSF and Brain from Patients with Different Brain Distributions of Pathological α-Synuclein in the Context of Co-Pathology and Non-LBD Diagnoses.Annals of neurology · 2022Article
- Autophagy mediates the clearance of oligodendroglial SNCA/alpha-synuclein and TPPP/p25A in multiple system atrophy models.Autophagy · 2022Article
- 1-Indanone and 1,3-indandione Derivatives as Ligands for Misfolded α-Synuclein Aggregates.ChemMedChem · 2022Article
- AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System.Frontiers in neurology · 2022Review
Corrections and comments
- Commented on by
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
aimsThe aim of this study was to test the hypothesis that different conformations of misfolded α-synuclein (α-syn) are present in Parkinson's disease (PD) brain.
methodsUsing two previously characterized conformations of α-syn fibrils, we generated new conformation-selective α-syn monoclonal antibodies (mAbs). We then interrogated multiple brain regions in a well-characterized autopsy cohort of PD patients (n = 49) with these mAbs, Syn7015 and Syn9029.
resultsSyn7015 detects Lewy bodies (LBs) and Lewy neurites (LNs) formed by pathological α-syn in all brain regions tested, and is particularly sensitive to LNs and small Lewy dots, inclusions believed to form early in the disease. Further, we observed colocalization between Syn7015 and an early marker of α-syn pathology formation, phospho-Ser129-α-syn, and a lack of extensive colocalization with markers of more mature pathology. In comparison, Syn9029 detects Lewy pathology in all regions examined, but indicates significantly fewer LNs than Syn7015. In addition, colocalization of Syn9029 with later markers of α-syn pathology maturation (ubiquitin and P62) suggests that the pathology detected by Syn9029 is older. Semiquantitative scoring of both LN and LB pathology in nine brain regions further established this trend, with Syn7015 LN scores consistently higher than Syn9029 LN scores.
conclusionsOur data indicate that different conformations of α-syn pathology are present in PD brain and correspond to different stages of maturity for Lewy pathology. Regional analysis of Syn7015 and Syn9029 immunostaining also provides support for the Braak hypothesis that α-syn pathology advances through the brain.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.