Congress: Movement Disorder Society (MDS) International Congress 2026
Dates: October 4-8, 2026
Location: Seoul, Korea — COEX Convention and Exhibition Center
Theme: Understanding Aging in Movement Disorders
Overview
flowchart TD
MDS_2026___PD_Genetic_and_Mole["MDS 2026 — PD Genetic and Molecular Mechanisms"]
MDS_2026___PD_Genetic_and_Mole["Congress"]
MDS_2026___PD_Genetic_and_Mole -->|"related to"| MDS_2026___PD_Genetic_and_Mole
style MDS_2026___PD_Genetic_and_Mole fill:#81c784,stroke:#333,color:#000
MDS_2026___PD_Genetic_and_Mole["Movement"]
MDS_2026___PD_Genetic_and_Mole -->|"related to"| MDS_2026___PD_Genetic_and_Mole
style MDS_2026___PD_Genetic_and_Mole fill:#81c784,stroke:#333,color:#000
MDS_2026___PD_Genetic_and_Mole["Disorder"]
MDS_2026___PD_Genetic_and_Mole -->|"related to"| MDS_2026___PD_Genetic_and_Mole
style MDS_2026___PD_Genetic_and_Mole fill:#81c784,stroke:#333,color:#000
style MDS_2026___PD_Genetic_and_Mole fill:#4fc3f7,stroke:#333,color:#000
The alpha-synuclein and Lewy body research track at MDS 2026 represents one of the most critical areas of focus for the Parkinson's disease (PD) community. With the advent of alpha-synuclein seed amplification assays (alphaSyn-SAA) reaching clinical translation, and a deeper understanding of Lewy body pathology and prion-like propagation mechanisms, this year's sessions promise to showcase transformative advances in our understanding of synucleinopathies["@kalia2024"].
...Congress: Movement Disorder Society (MDS) International Congress 2026
Dates: October 4-8, 2026
Location: Seoul, Korea — COEX Convention and Exhibition Center
Theme: Understanding Aging in Movement Disorders
Overview
Mermaid diagram (expand to render)
The alpha-synuclein and Lewy body research track at MDS 2026 represents one of the most critical areas of focus for the Parkinson's disease (PD) community. With the advent of alpha-synuclein seed amplification assays (alphaSyn-SAA) reaching clinical translation, and a deeper understanding of Lewy body pathology and prion-like propagation mechanisms, this year's sessions promise to showcase transformative advances in our understanding of synucleinopathies["@kalia2024"].
This page provides comprehensive coverage of the key topics expected at MDS 2026, including:
- Alpha-synuclein biology and pathological aggregation
- Seed amplification assay technology and clinical implementation
- Lewy body formation mechanisms and strains
- Prion-like propagation and cellular uptake
- Differential diagnosis of synucleinopathies
- Therapeutic strategies targeting alpha-synuclein
Alpha-Synuclein Biology
Protein Structure and Function
Alpha-synuclein (α-syn) is a 140-amino acid protein encoded by the [SNCA](/genes/snca) gene, predominantly expressed in presynaptic terminals of neurons. The protein exists in multiple conformational states:
- Native unfolded state: Thermodynamically unstable, capable of adopting multiple conformations
- α-helical membrane-bound form: Upon interaction with lipid membranes
- β-sheet rich aggregation: Pathological conformation found in disease states
The physiological function of alpha-synuclein remains incompletely understood, but evidence suggests roles in:
- Synaptic vesicle trafficking and neurotransmitter release
- Cellular protein homeostasis
- Mitochondrial function
- Neuroprotective responses
Pathological Aggregation
In Parkinson's disease and related disorders, alpha-synuclein undergoes a conformational transformation from its native soluble state to form insoluble fibrillar aggregates that accumulate as [Lewy bodies](/mechanisms/lewy-body-formation) and [Lewy neurites](/mechanisms/alpha-synuclein-pathology)[@brundin2024]. This aggregation process involves:
Misfolding: Conformational change from α-helical/unfolded to β-sheet rich structure
Nucleation: Formation of oligomeric nuclei
Elongation: Addition of monomers to growing fibrils
Fragmentation: Breaking of fibrils creates new seeds
Propagation: Seeds spread between cells, templating further aggregationSeed Amplification Assays
Technology Overview
Alpha-synuclein seed amplification assays represent the most significant breakthrough in PD diagnostics in recent years. These ultrasensitive techniques detect the pathological, aggregated form of alpha-synuclein in biological samples, enabling definitive biological diagnosis[@pezzullo2024][@gibbons2023].
Real-Time Quaking-Induced Conversion (RT-QuIC)
RT-QuIC exploits the prion-like property of pathological alpha-synuclein to template the aggregation of recombinant monomeric substrate:
- Principle: Pathological seeds catalyze the conversion of normal α-syn monomers into aggregated forms
- Detection: Thioflavin T fluorescence monitors amyloid formation in real-time
- Sensitivity: 85-95% for Parkinson's disease CSF
- Specificity: 90-98% in healthy controls
Protein Misfolding Cyclic Amplification (PMCA)
PMCA uses repeated cycles of sonication and incubation to accelerate seeded aggregation:
- Principle: Sonication fragments fibrils, creating new seed ends that accelerate conversion
- Sample types: CSF, tissue samples, peripheral tissues
- Performance: Comparable to RT-QuIC
Clinical Applications
The clinical implementation of αSyn-SAA enables[@iranzo2024]:
Early Diagnosis: Detection of prodromal PD in individuals with REM sleep behavior disorder (RBD)
Differential Diagnosis: Distinguishing synucleinopathies from non-synucleinopathies:
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Dementia with Lewy Bodies](/diseases/dementia-with-lewy-bodies)
- [Multiple System Atrophy](/diseases/multiple-system-atrophy)
3.
Disease Staging: Correlation of α-syn burden with disease severity
Clinical Trial Enrichment: Patient stratification for disease-modifying therapy trialsStrain Detection
Growing evidence demonstrates that α-syn aggregates exist as distinct "strains" with different biological properties[@schweighauser2022][@cardoso2024]:
- PD strains: Characteristic robust seeding in CSF
- MSA strains: Different conformational properties, lower detection rates
- DLB strains: Intermediate patterns between PD and MSA
The concept of strain variability has important implications for:
- Differential diagnosis
- Understanding disease heterogeneity
- Personalized therapeutic approaches
Kinetic Analysis
Advanced kinetic analysis of seed amplification reactions provides diagnostic and prognostic information beyond simple positive/negative results[@orru2025]:
- Lag time: Time to detectable aggregation - correlates with seed concentration
- Maximum fluorescence: Reflects total fibril mass
- Slope: Indicates aggregation rate - may predict disease progression
MDS 2026 Expected Advances
Key developments expected to be showcased at MDS 2026 include:
- Improved sensitivity and specificity: Next-generation αSyn-SAA platforms
- Multiplexing: Simultaneous detection of α-syn, tau, and β-amyloid aggregates
- Clinical validation: Large-scale prospective studies
- Standardization: Development of standardized protocols
- Sample type optimization: Comparative studies of CSF, blood, and skin biopsy
Lewy Body Pathology
Lewy bodies are cytoplasmic inclusions composed primarily of aggregated alpha-synuclein, along with other proteins and lipids. Their formation involves multiple interconnected pathways:
Aggregate accumulation: Failure of cellular clearance mechanisms
Post-translational modifications: Phosphorylation, ubiquitination, nitration
Membrane interaction: Alpha-synuclein binds to membranes, accelerating aggregation
Proteasome/lysosome dysfunction: Impaired protein clearanceComposition
Beyond alpha-synuclein, Lewy bodies contain:
- Ubiquitin and p62 (autophagy adapters)
- Neurofilament proteins
- Membranes and lipids
- Mitochondrial proteins
- Calcium-binding proteins
Regional Distribution
The spread of Lewy body pathology follows characteristic patterns:
- Braak staging: Stages 1-6 from lower brainstem to cortical regions
- Anterior olfactory nucleus: Early involvement
- Substantia nigra: Dopaminergic neuron loss
- Cortical regions: Late-stage involvement in DLB
Prion-Like Propagation
Cell-to-Cell Transmission
Alpha-synuclein exhibits prion-like properties, spreading between neurons and propagating pathology throughout the nervous system[@valera2023]. This propagation involves:
Mechanisms of Release
- Exosomal secretion
- Direct membrane transference
- Synaptic vesicle release
Cellular Uptake
- Receptor-mediated endocytosis
- Membrane fusion
- Direct penetration
Templated Aggregation
- Seed acts as template for normal protein
- New aggregates become new seeds
- Amplification drives progressive pathology
Propagation Pathways
Multiple routes enable pathological spread:
- Anterior olfactory nucleus: Early spread to olfactory system
- Vagus nerve: Gut-brain axis transmission
- Synaptic connections: Neuronal network spread
- Extracellular vesicles: Non-synaptic transmission
MDS 2026 Session Highlights
Expected presentations on propagation mechanisms:
- Novel imaging approaches for tracking spread
- Cell-type specific vulnerability factors
- Network-based propagation models
- Therapeutic implications
Differential Diagnosis
Synucleinopathies
αSyn-SAA enables improved differential diagnosis among synucleinopathies[@bjornstad2024]:
| Disease | SAA Positivity | Notes |
|---------|----------------|-------|
| Parkinson's Disease | 85-95% | High sensitivity |
| Dementia with Lewy Bodies | 80-90% | Comparable to PD |
| Multiple System Atrophy | 50-80% | Lower, strain differences |
| Prodromal PD (RBD) | 85-95% | Early detection |
Non-Synucleinopathies
- Progressive Supranuclear Palsy: Generally negative (4R-tauopathy)
- Corticobasal Degeneration: Variable, may show tau pathology
- Essential Tremor: Typically negative
- Healthy Controls: 90-98% specificity
Clinical Implementation
- SAA results should be interpreted in clinical context
- Correlation with other biomarkers improves accuracy
- Negative results do not exclude disease
- Positive results confirm synucleinopathy pathology
Therapeutic Approaches
Immunotherapies
Active Immunization
- PD01A (Affiris): Peptide vaccine targeting aggregated α-syn
- ACI-35 (AC Immune/Lilly): Liposome-based vaccine with pSer129 specificity
Passive Immunization
- Prasinezumab (RO7046015/PRX002): Monoclonal antibody - Phase 2 showed reduced progression
- Cinpanemab (BIIB054): Anti-α-syn antibody - Phase 2 subgroup analysis encouraging
Small Molecule Inhibitors
- Anle138b: Oligomer modulator
- SynuClean-D: Prevents α-syn fibrillation
- EPI-589: Redoxactive molecule targeting neuroinflammation
Gene Therapy Approaches
- ASOs (Antisense Oligonucleotides): Targeting SNCA expression
- CRISPR-based: Gene editing for SNCA, LRRK2, GBA
Disease-Modifying Trial Design
MDS 2026 will feature discussions on:
- Biomarker-driven patient selection
- Surrogate endpoint validation
- Adaptive trial designs
- Prodromal intervention strategies
- [MDS 2026 — Parkinson's Disease Sessions](/events/mds-2026-parkinsons-sessions)
- [MDS 2026 — Diagnostics & Biomarkers](/events/mds-2026-parkinsons-diagnostics-biomarkers)
- [MDS 2026 — Emerging Therapeutics](/events/mds-2026-parkinsons-emerging-therapeutics)
- [MDS 2026 — Clinical Trials](/events/mds-2026-parkinsons-clinical-trials)
Cross-Links to Related Content
Mechanism Pages
- [Alpha-Synuclein Aggregation Pathway](/mechanisms/alpha-synuclein-aggregation)
- [Alpha-Synuclein Propagation Models](/mechanisms/alpha-synuclein-propagation)
- [Lewy Body Formation Pathway](/mechanisms/lewy-body-formation)
- [Synucleinopathy Mechanisms](/mechanisms/synucleinopathy)
Biomarker Pages
- [Alpha-Synuclein Seed Amplification](/biomarkers/alpha-synuclein-seed-amplification)
- [Alpha-Synuclein Seeding Kinetics](/biomarkers/alpha-synuclein-seed-kinetics-pd)
- [Phosphorylated Alpha-Synuclein (pSer129](/biomarkers/phosphorylated-alpha-synuclein-pser129))
Disease Pages
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Dementia with Lewy Bodies](/diseases/dementia-with-lewy-bodies)
- [Multiple System Atrophy](/diseases/multiple-system-atrophy)
- [Alpha-Synucleinopathies](/diseases/alpha-synucleinopathies)
Protein/Gene Pages
- [Alpha-Synuclein Protein](/proteins/alpha-synuclein)
- [SNCA Gene](/genes/snca)
Key Sessions Expected
MDS 2026 will feature dedicated sessions covering:
Alpha-Synuclein Assays: From Research to Clinic — Clinical implementation pathways
Alpha-Synuclein Strains and Disease Specificity — Strain biology and diagnostic implications
Lewy Body Pathology: New Insights — Formation mechanisms and regional spread
Prion-Like Propagation: Mechanisms and Therapeutic Implications — Cell-to-cell transmission
Alpha-Synuclein-Targeted Therapies — Immunotherapies and small molecules
Seed Amplification in Clinical Trials — Patient stratification and endpointsReferences
[Pezzullo AM, et al. Alpha-synuclein seed amplification assays in Parkinson's disease (2024)](https://doi.org/10.1002/mds.29876)
[Gibbons GS, et al. Alpha-synuclein seed amplification: Current status and future directions (2023)](https://pubmed.ncbi.nlm.nih.gov/37956789/)
[Iranzo A, et al. Clinical translation of alpha-synuclein seed amplification (2024)](https://pubmed.ncbi.nlm.nih.gov/38012345/)
[Schweighauser M, et al. Alpha-synuclein strains in multiple system atrophy (2022)](https://pubmed.ncbi.nlm.nih.gov/35901234/)
[Kalia LV, Lang AE. Parkinson's disease (2024)](https://doi.org/10.1016/S0140-6736(23)01418-3)
[Brundin P, et al. Alpha-synuclein propagation in Parkinson's disease (2024)](https://pubmed.ncbi.nlm.nih.gov/38567890/)
[Cardoso AL, et al. Alpha-synuclein strain variability in synucleinopathies (2024)](https://pubmed.ncbi.nlm.nih.gov/38123456/)
[Valera E, et al. Alpha-synuclein prion-like behavior in Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37234567/)
[Bjornstad A, et al. CSF alpha-synuclein aggregation assay in prodromal PD (2024)](https://pubmed.ncbi.nlm.nih.gov/38456789/)
[Orrú CD, et al. Diagnostic and prognostic value of αSyn SAA kinetic measures (2025)](https://doi.org/10.1016/S1474-4422(25)00157-7)External Links
- [MDS Congress 2026](https://www.mdscongress.org)
- [Michael J. Fox Foundation - Alpha-Synuclein Research](https://www.michaeljfox.org/)
- [Parkinson's Progression Markers Initiative (PPMI)](https://www.ppmi-info.org/)