ArticleProceedings of the National Academy of Sciences of the United States of America2019
α-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Co- and Multi-Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Blood-Based α-Synuclein Biomarkers in Parkinson's Disease: Molecular Diversity, Analytical Advances and Clinical Translation.International journal of molecular sciences · 2026Review
- The APOA1-SNCA Axis as a Molecular Bridge Between CKD and Parkinson's Disease: A Systems Biology Model of Kidney-to-Brain Propagation via Exosomal Pathways.International journal of molecular sciences · 2026Article
- Gut-initiated alpha synuclein fibrils drive parkinsonism phenotypes: temporal mapping of REM sleep behavior disorder-like and other non-motor symptoms.Translational neurodegeneration · 2026Article
- In situ NMR and integrative proteomics reveal the interaction signature of serum α-synuclein.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Age-(in)dependent altered molecular mechanisms in Parkinson's disease through extracellular vesicle proteome and lipidome.Cell reports. Medicine · 2025Article
- Lipid metabolism in microglia: Emerging mechanisms and therapeutic opportunities for neurodegenerative diseases (Review).International journal of molecular medicine · 2025Review
- Expanding our understanding of synucleinopathies: proteinopathy, proteinopenia, and lipidopathy.The FEBS journal · 2025Review
- The Emerging Role of the Molecular Chaperone Clusterin in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Cutaneous nerve fiber pathology and function in Parkinson's disease and atypical parkinsonism - a cohort study.NPJ Parkinson's disease · 2025Article
- Enhanced serum-based seed amplification assay for detecting propagative α-synuclein seeds in Parkinson's disease.Translational neurodegeneration · 2025Article
- Parkinson disease-associated toxic exposures selectively up-regulate vesicular glutamate transporter vGlut2 in a model of human cortical neurons.Molecular biology of the cell · 2025Article
- The role ofFrontiers in neuroscience · 2025Review
- Engineered sequestrins inhibit aggregation of pathogenic alpha-synuclein mutants.Frontiers in immunology · 2025Article
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Role of Lipids in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- Secretome Analyses Identify FKBP4 as aInternational journal of molecular sciences · 2024Article
- Elevated ApoE, ApoJ and lipoprotein-bound α-synuclein levels in cerebrospinal fluid from Parkinson's disease patients - Validation in the BioFIND cohort.Parkinsonism & related disorders · 2023Article
- Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson's disease.Translational neurodegeneration · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The progressive accumulation, aggregation, and spread of α-synuclein (αSN) are common hallmarks of Parkinson's disease (PD) pathology. Moreover, numerous proteins interact with αSN species, influencing its toxicity in the brain. In the present study, we extended analyses of αSN-interacting proteins to cerebrospinal fluid (CSF). Using coimmunoprecipitation, followed by mass spectrometry, we found that αSN colocalize with apolipoproteins on lipoprotein vesicles. We confirmed these interactions using several methods, including the enrichment of lipoproteins with a recombinant αSN, and the subsequent uptake of prepared vesicles by human dopaminergic neuronal-like cells. Further, we report an increased level of ApoE in CSF from early PD patients compared with matched controls in 3 independent cohorts. Moreover, in contrast to controls, we observed the presence of ApoE-positive neuromelanin-containing dopaminergic neurons in substantia nigra of PD patients. In conclusion, the cooccurrence of αSN on lipoprotein vesicles, and their uptake by dopaminergic neurons along with an increase of ApoE in early PD, proposes a mechanism(s) for αSN spreading in the extracellular milieu of PD.
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