MDS 2026 — Alpha-Synuclein & Lewy Body Research

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

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

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

• 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:

Seed 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]:

• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Dementia with Lewy Bodies](/diseases/dementia-with-lewy-bodies)
• [Multiple System Atrophy](/diseases/multiple-system-atrophy)

Strain 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

• 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

Formation Mechanisms

Lewy bodies are cytoplasmic inclusions composed primarily of aggregated alpha-synuclein, along with other proteins and lipids. Their formation involves multiple interconnected pathways:

Composition

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

Related Sessions at MDS 2026

• [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:

References

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/)