ArticleNPJ Parkinson's disease2023
Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases.
Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- Probing the Energy Landscape of α-Synuclein Amyloid Fibril Formation by Systematic K-to-Q Mutagenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholesterol dysregulation in APOE4 astrocytes promotes α-synuclein pathology in miBrains.Cell stem cell · 2026Article
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson's disease.Nature communications · 2026Article
- Large-scale visualization of α-synuclein oligomers in Parkinson's disease brain tissue.Nature biomedical engineering · 2026Article
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- Highly sensitive chemiluminescence imaging of misfolded proteins in neurodegenerative models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synaptic Vesicle Disruption in Parkinson's Disease: Dual Roles of α-Synuclein and Emerging Therapeutic Targets.Brain sciences · 2025Review
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
- Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses.NPJ Parkinson's disease · 2025Article
- Synaptic vesicle endocytosis deficits underlie cognitive dysfunction in mouse models of GBA-linked Parkinson's disease and dementia with Lewy bodies.Nature communications · 2025Article
- Recombinant cathepsins B and L promote α-synuclein clearance and restore lysosomal function in human and murine models with α-synuclein pathology.Molecular neurodegeneration · 2025Article
- Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation.NPJ Parkinson's disease · 2025Article
- Synaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson's disease.Nature communications · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- Abnormal α-synuclein binds to synaptotagmin 13, impairing extracellular vesicle release in synucleinopathies.Translational neurodegeneration · 2025Article
- α-Synuclein Pathology in Synucleinopathies: Mechanisms, Biomarkers, and Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Multiplex Immunofluorescent Analysis of Alpha-Synuclein in Nigral Lewy Bodies With Heat-Induced Antibody Stripping Reveals an Intricate Multilayered Structure.Neuropathology and applied neurobiology · 2025Article
- Huntingtin inclusion bodies have distinct immunophenotypes and ubiquitination profiles in the Huntington's disease human cerebral cortex.Scientific reports · 2025Article
- Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy.Nature communications · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance among these disorders. Relying on antibodies that have not been assessed for their ability to detect the diverse forms of aSyn may lead to inaccurate estimations of aSyn pathology in human brains or disease models. To address this challenge, we developed and characterized an expanded antibody panel that targets different sequences and post-translational modifications along the length of aSyn, and that recognizes all monomeric, oligomeric, and fibrillar aSyn conformations. Next, we profiled aSyn pathology across sporadic and familial Lewy body diseases (LBDs) and reveal heterogeneous forms of aSyn pathology, rich in Serine 129 phosphorylation, Tyrosine 39 nitration and N- and C-terminal tyrosine phosphorylations, scattered both to neurons and glia. In addition, we show that aSyn can become hyperphosphorylated during processes of aggregation and inclusion maturation in neuronal and animal models of aSyn seeding and spreading. The validation pipeline we describe for these antibodies paves the way for systematic investigations into aSyn pathological diversity in the human brain, peripheral tissues, as well as in cellular and animal models of synucleinopathies.
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Registered trials
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