ArticleNPJ Parkinson's disease2022
Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.
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 43 papers.
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43 citing papers in PubMed, 63 citations in OpenAlex.
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- α-Synuclein aggregation landscape from phase separation to neurotoxic intermediates.FEBS letters · 2026Review
- Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson's disease.Nature communications · 2026Article
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Cross-Linking and Covalent Labeling Mass Spectrometry Reveal Proteoform-Driven Conformational Changes in Alpha Synuclein.Analytical chemistry · 2026Article
- Evaluation of an antibody panel for alpha-synuclein detection in FFPE rectal biopsies in Parkinson's disease.IBRO neuroscience reports · 2025Article
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- C-terminus-dependent detection of lysosomal alpha-synuclein in nigral Parkinson's disease human brain neurons.Molecular neurodegeneration · 2025Article
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- In vivo validation of novel non-invasive PHP.eB AAVs as a potential therapeutic approach for alpha-synucleinopathies.Acta neuropathologica communications · 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
- Phosphorylated α-synuclein in CSF and plasma does not reflect synucleinopathy.NPJ Parkinson's disease · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- 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
- Phosphorylated alpha-synuclein distribution in the colonic enteric nervous system of patients with diverticular disease.IBRO neuroscience reports · 2025Article
- Neural-induced human adipose tissue-derived stem cell secretome exerts neuroprotection against rotenone-induced Parkinson's disease in rats.Stem cell research & therapy · 2025Article
- Female mice exhibit resistance to disease progression despite early pathology in a transgenic mouse model inoculated with alpha-synuclein fibrils.Communications biology · 2025Article
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibodies against phosphorylated alpha-synuclein (aSyn) at S129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson's disease and other neurodegenerative diseases. Herein, we demonstrate that the co-occurrence of multiple pathology-associated C-terminal post-translational modifications (PTMs) (e.g., phosphorylation at Tyrosine 125 or truncation at residue 133 or 135) differentially influences the detection of pS129-aSyn species by pS129-aSyn antibodies. These observations prompted us to systematically reassess the specificity of the most commonly used pS129 antibodies against monomeric and aggregated forms of pS129-aSyn in mouse brain slices, primary neurons, mammalian cells and seeding models of aSyn pathology formation. We identified two antibodies that are insensitive to pS129 neighboring PTMs. Although most pS129 antibodies showed good performance in detecting aSyn aggregates in cells, neurons and mouse brain tissue containing abundant aSyn pathology, they also showed cross-reactivity towards other proteins and often detected non-specific low and high molecular weight bands in aSyn knock-out samples that could be easily mistaken for monomeric or high molecular weight aSyn species. Our observations suggest that not all pS129 antibodies capture the biochemical and morphological diversity of aSyn pathology, and all should be used with the appropriate protein standards and controls when investigating aSyn under physiological conditions. Finally, our work underscores the need for more pS129 antibodies that are not sensitive to neighboring PTMs and more thorough characterization and validation of existing and new antibodies.
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