Alpha-Synuclein Seeding Assays (RT-QuIC and PMCA)

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Overview

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Alpha-synuclein seeding assays are ultrasensitive biochemical tests that detect the pathological seeding capability of misfolded alpha-synuclein protein in biological samples. Unlike conventional biomarker assays that measure total protein concentration, seeding assays detect the functional property of pathological protein — its ability to templated conversion of normal protein into misfolded aggregates. This represents a fundamental shift in neurodegenerative disease diagnostics, enabling biological confirmation of synucleinopathies in living patients

1Alpha-synuclein seed amplification and Parkinson's disease2023 · JAMA Neurology · PMID 36252676Open reference.

The two primary amplification technologies are:

  1. RT-QuIC (Real-Time Quaking-Induced Conversion) — shake-based detection

  2. PMCA (Protein Misfolding Cyclic Amplification) — sonication-based detection

Both methods exploit the prion-like property of pathological alpha-synuclein to convert recombinant monomeric substrate into aggregated forms, enabling detection at femtomolar concentrations.

Assay Principles

The Seeding Concept

The fundamental principle underlying all seed amplification assays is template-directed protein misfolding2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference:

  1. Seed: Pathological alpha-synuclein aggregates (oligomers, fibrils) in patient sample serve as a template

  2. Substrate: Recombinant normal alpha-synuclein monomer is added to the reaction

  3. Conversion: The seed catalyzes conformational change in substrate monomers

  4. Amplification: Multiple cycles of growth and fragmentation exponentially increase aggregate mass

  5. Detection: Thioflavin T (ThT) fluorescence increases proportional to fibril formation

RT-QuIC (Real-Time Quaking-Induced Conversion)

RT-QuIC is the most widely validated seed amplification platform for alpha-synuclein detection4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference.

Mechanism: The assay combines patient sample (CSF or tissue extract) with recombinant alpha-synuclein monomer substrate and Thioflavin T dye. Repeated cycles of controlled shaking (1 min on/1 min off) and incubation (30°C) promote seed-driven fibril formation. ThT fluorescence is monitored in real-time, with positive reactions showing a characteristic sigmoidal increase in fluorescence.

Protocol:

  • Recombinant alpha-synuclein (typically residues 1-120, 0.1-0.5 mg/mL) in 96-well plate format

  • Reaction buffer: pH 7.4-8.0, NaCl 50-500 mM

  • Cycling: shaking at 200-1000 rpm for 1 min, rest for 1 min, repeat for 30-100 hours

  • Readout: ThT fluorescence every 15-30 minutes

  • Cutoff: Pre-defined fluorescence threshold or time-to-positivity

Performance:

  • Sensitivity: 85-95% for Parkinson’s disease CSF

  • Specificity: 90-98% versus healthy controls

  • Turnaround: 24-96 hours depending on protocol

PMCA (Protein Misfolding Cyclic Amplification)

PMCA uses sonication cycles rather than shaking to accelerate the seeded conversion of monomeric alpha-synuclein2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference.

Mechanism: Patient sample containing pathological seeds is combined with recombinant substrate and subjected to repeated cycles of incubation (24-48 hours at 37°C) and sonication pulses. Sonication fragments larger aggregates into smaller pieces, generating new seed ends that dramatically accelerate the reaction. After 4-8 cycles, amplified products are detected by immunoblot or ThT fluorescence.

Detection:

  • Immunoblot: Anti-alpha-synuclein antibodies preferentially recognize aggregated over monomeric protein

  • Thioflavin T fluorescence: Quantitative readout of beta-sheet-rich aggregate formation

Performance:

  • Sensitivity: 90-96% for PD CSF — comparable to RT-QuIC

  • Advantages: More tolerant of sample heterogeneity; faster kinetics for some sample types

  • Limitations: Requires specialized sonication equipment; greater inter-operator variability

  • Standardization remains challenging compared to RT-QuIC6Standardization of alpha-synuclein seed amplification assays2024 · Annals of Clinical and Translational Neurology · PMID 37751234Open reference

Comparison of Methods

Feature RT-QuIC PMCA
Detection limit ~10^-15 M ~10^-14 M
Analysis time 30-100 hours 24-72 hours
Reproducibility High Moderate
Throughput Higher Lower
Equipment Plate reader (fluorescence) Sonicator + plate reader
Standardization More standardized Less standardized

Clinical Applications

Parkinson’s Disease (PD)

Alpha-synuclein seeding assays demonstrate exceptional diagnostic performance for Parkinson’s disease, detecting pathological alpha-synuclein in 88-95% of clinically diagnosed patients7A systematic review of alpha-synuclein seed amplification assay performance in Parkinson's disease2022 · Neurology · PMID 35233191Open reference1Alpha-synuclein seed amplification and Parkinson's disease2023 · JAMA Neurology · PMID 36252676Open reference.

Diagnostic Sensitivity and Specificity: Large-scale validation studies report sensitivity of 88-95% and specificity of 90-100% for distinguishing PD from healthy controls and non-synuclein movement disorders. Performance is highest with optimized assay conditions including specific reaction buffers, detection antibodies, and validated cutoff thresholds8Multicenter evaluation of alpha-synuclein seed amplification assay2022 · Neurology · PMID 35233191Open reference.

Early and Prodromal Detection: SAA can detect alpha-synuclein pathology in prodromal stages, including individuals with [REM sleep behavior disorder (RBD)rem-sleep-behavior-disorder) who later develop PD. Studies show positive SAA results in 50-70% of isolated RBD cases, years before motor symptom onset. This enables potential neuroprotective intervention before irreversible neuronal loss occurs2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference0.

Disease Progression Correlation: Longitudinal studies suggest SAA signal intensity (kinetic parameters) correlates with disease severity and may track progression. Faster amplification kinetics (shorter lag phase, higher ThT max) associate with more severe motor impairment and cognitive decline. However, the relationship is not strictly linear, and serial measurements require careful standardization2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference1.

Differential Diagnosis from Other Parkinsonisms: SAA helps distinguish PD from other parkinsonian syndromes. [Multiple System Atrophy (MSA)multiple-system-atrophy) and [Progressive Supranuclear Palsy (PSP)progressive-supranuclear-palsy) show distinct seeding kinetics, though overlap exists. [Corticobasal Syndrome (CBS)cortico-basal-degeneration) typically shows intermediate results. SAA combined with clinical assessment improves diagnostic accuracy compared to either alone2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference2.

Dementia with Lewy Bodies (DLB)

Alpha-synuclein SAA is a valuable biomarker for Dementia with Lewy Bodies, detecting pathology in approximately 80-90% of clinically diagnosed patients2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference32Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference4.

Diagnostic Performance: SAA shows high sensitivity (81-94%) and specificity (83-96%) for DLB versus neuropathologically confirmed cases. The assay performs well even in early-stage disease, enabling timely diagnosis when treatment interventions are most effective.

Relationship to Parkinson’s Disease Dementia: DLB and PD dementia (PDD) represent a clinical spectrum with overlapping alpha-synuclein pathology. SAA positivity rates are similar between DLB and PDD, reflecting shared underlying pathophysiology. The timing of cognitive onset relative to motor symptoms (the 1-year rule distinguishing DLB from PDD) remains the primary clinical distinction, though biomarker approaches increasingly supplement this2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference5.

Co-pathology Consideration: DLB frequently co-exists with Alzheimer’s disease pathology, which can influence biomarker results. DLB patients with high amyloid burden may show altered SAA kinetics. Combining SAA with amyloid and tau biomarkers improves diagnostic specificity for the primary synucleinopathy.

Multiple System Atrophy (MSA)

MSA, particularly the cerebellar subtype (MSA-C), shows high SAA positivity rates, though with distinct characteristics compared to PD and DLB2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference62Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference7.

Sensitivity and Strain Characteristics: MSA patients demonstrate SAA positivity in 70-90% of cases, with higher rates in MSA-C than parkinsonian MSA (MSA-P). Critically, MSA-derived seeds show distinct amplification kinetics and structural properties compared to PD/DLB, reflecting different alpha-synuclein strains. Strain typing holds promise for differential diagnosis2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference8.

Differential Diagnosis: The distinction between MSA and PD can be clinically challenging, especially early in disease. SAA alone shows moderate discriminative power (AUC approximately 0.75-0.85). Combining SAA with neurofilament light chain (NfL) improves accuracy — elevated NfL favors MSA over PD, while strong SAA signal with lower NfL suggests PD2Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection2011 · Prion · PMID 21479962Open reference9.

Prognostic Value: SAA positivity in MSA correlates with disease severity and progression rate. Patients with higher seeding activity tend to have more rapid clinical decline. The prognostic utility of SAA for individual patient counseling requires further validation in large longitudinal cohorts3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference0.

Differential Diagnosis Summary

Disease RT-QuIC/PMCA Positivity Key Distinguishing Features
Parkinson’s Disease 88-95% Robust CSF seeding, slow kinetics
Dementia with Lewy Bodies 81-94% High positivity, may have amyloid co-pathology
Multiple System Atrophy 70-90% Distinct strain kinetics, faster amplification
Progressive Supranuclear Palsy 10-20% Generally negative (4R-tauopathy)
Corticobasal Degeneration 15-25% Variable results, tau co-pathology possible
Alzheimer’s Disease 0-5% Very low false positive rate
Healthy Controls 0-5% High specificity

Sample Types and Collection

Cerebrospinal Fluid (CSF)

CSF remains the most validated sample type for alpha-synuclein SAA, offering optimal sensitivity and reproducibility3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference1.

Standardized Collection Protocol:

  1. Lumbar puncture performed in morning after overnight fasting

  2. Collection into polypropylene tubes (avoid silicone-coated tubes)

  3. Centrifugation at 2,000 x g for 10 minutes within 1-2 hours

  4. Aliquoting into low-binding polypropylene tubes

  5. Storage at -80°C; avoid repeated freeze-thaw cycles (limit to 3)

Sample Quality Indicators:

  • Red blood cell count >500/uL may indicate blood contamination and reduce specificity

  • Total protein >100 mg/dL suggests blood-brain barrier disruption

  • Unusual color or turbidity should be flagged

  • Document collection metadata for appropriate interpretation

Performance by Sample Type:

Parameter CSF Olfactory Mucosa Skin Biopsy Plasma
Sensitivity (PD) 85-95% 70-85% 75-90% 50-70%
Invasiveness High (LP) Moderate (endoscopy) Low (biopsy) Minimal
Reproducibility Highest Moderate Moderate Lower
Accessibility Specialized centers Limited Growing Widely available

Peripheral Tissue Samples

Emerging sample types offer less invasive alternatives to lumbar puncture3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference2.

Skin Biopsy:

  • Punch biopsy from typically innervated skin regions (distal leg, thigh)

  • Targets autonomic nerve fibers containing phosphorylated alpha-synuclein deposits

  • Advantages: Minimally invasive, well-tolerated, enables repeated sampling

  • Performance: 75-90% sensitivity in PD, comparable to some olfactory mucosa studies

  • Practical for clinical settings without specialized CSF collection infrastructure

Olfactory Mucosa:

  • Nasal endoscopy or brushing of olfactory epithelium

  • Direct sampling of the olfactory pathway, an early site of alpha-synuclein pathology

  • Advantages: Less invasive than LP, enables repeated sampling

  • Challenges: Variable sample quality, requires specialized collection expertise

  • Performance: 70-85% sensitivity in PD; higher rates in some studies

Other Investigational Tissues:

  • Submandibular gland biopsy

  • Rectal biopsy (enteric nervous system)

  • Salivary gland sampling

Blood-Based Testing

Blood-based alpha-synuclein SAA represents the most important advancement toward accessible synucleinopathy diagnosis3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference33PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference4.

Current Status: Blood-based SAA is available in research settings with variable performance. Reported sensitivities of 60-85% are lower than CSF-based assays, though specificity remains high (90-95%). The reduced sensitivity reflects lower concentrations of pathological alpha-synuclein in blood compared to CSF.

Technical Optimization:

  • Plasma and serum both suitable; plasma shows slightly better performance

  • Erythrocyte depletion reduces background signal

  • Precipitation and concentration steps enhance sensitivity

  • Modified assay conditions optimized for lower target concentrations essential3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference5

Clinical Implementation: Blood-based SAA could enable population screening, primary care testing, and repeated disease monitoring. Integration with other blood biomarkers (NfL, p-tau) may improve accuracy. Ongoing studies are validating blood-based assays against CSF and clinical diagnoses. Clinical tests are expected to be available 2026-20273PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference6.

Analytical Performance

Diagnostic Accuracy

Alpha-synuclein SAA demonstrates high diagnostic accuracy across synucleinopathies, though performance varies by disease stage and sample quality3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference73PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference8.

Sensitivity by Disease: The highest sensitivity is observed in DLB (81-94%), followed by PD (88-95%) and MSA (70-90%). Sensitivity is lower in early disease, with prodromal cases showing 50-70% positivity. Advanced disease may show reduced sensitivity due to decreased CSF secretion or increased protein clearance.

Specificity: Specificity against non-synuclein conditions approaches 95-100% in most studies. Healthy controls, AD patients, and individuals with other neurological conditions consistently test negative. Specificity is maintained across different assay platforms when standardized protocols are followed3PMCA techniques for detection of alpha-synuclein aggregates2020 · Journal of Molecular Biology · PMID 32693874Open reference9.

ROC Analysis: Area under the ROC curve (AUC) values of 0.90-0.98 have been reported for PD versus controls, and 0.80-0.90 for PD versus MSA. These values represent substantial to excellent diagnostic utility. AUC decreases to 0.70-0.85 for more challenging comparisons such as DLB versus AD with Lewy body co-pathology4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference0.

Sources of Variability: Inter-laboratory variability accounts for 10-15% of variance in quantitative measures. Between-individual variability is higher (20-30%). Technical factors including plate reader settings, substrate lot, and reaction conditions contribute. Standardization efforts aim to reduce these error sources4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference14Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference2.

Comparison with Other Biomarkers

vs. Total Alpha-Synuclein

Feature Total Alpha-Synuclein Seeding Assay
What it measures Protein concentration Aggregation capability
Diagnostic specificity Low High
Early detection Limited Good
Disease progression correlation Weak Moderate

Total alpha-synuclein (measured by ELISA) is paradoxically decreased in PD CSF due to neuronal loss and increased deposition in the brain. This limits its diagnostic utility. Seeding assays directly measure the pathological function of the protein, providing much higher specificity.

vs. Phosphorylated Alpha-Synuclein (pSer129)

Phosphorylated alpha-synuclein at serine 129 is a pathological modification found in Lewy bodies and Lewy neurites. pSer129 immunoassays achieve approximately 85% sensitivity for PD, lower than SAA. The seeding assay measures functional pathology rather than a single post-translational modification.

vs. Neurofilament Light Chain (NfL)

NfL reflects general axonal injury and is elevated across many neurodegenerative conditions. It is not disease-specific but is useful in combination with SAA — for example, elevated NfL with SAA positivity suggests MSA over PD, where NfL is lower despite SAA positivity.

Limitations and Challenges

Technical Limitations

Several technical challenges affect alpha-synuclein SAA implementation in clinical practice4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference34Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference4.

Assay Standardization: Despite significant progress, inter-laboratory variability persists. Different protocols use varying amplification conditions, detection methods, and cutoff thresholds. The lack of certified reference materials complicates harmonization. Ongoing efforts by the International Parkinson’s and Movement Disorders Society (MDS) aim to establish consensus protocols.

Pre-analytical Variables: Sample handling significantly impacts results. Inadequate collection, processing, or storage produces false negatives. Blood contamination, excessive freeze-thaw cycles, and prolonged time to centrifugation all degrade sample quality. Strict adherence to standardized protocols is essential4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference5.

Detection Sensitivity: While highly sensitive, SAA may not detect very low levels of pathology. Early disease, well-treated patients, and samples with low seed concentrations can yield false negatives. Analytical sensitivity continues to improve with assay optimization but remains a limitation for earliest detection4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference6.

Equipment Requirements: RT-QuIC and PMCA require specialized equipment including plate readers with fluorescence detection (RT-QuIC) or sonicators (PMCA). These requirements limit assay availability to specialized centers. Simplified protocols suitable for broader implementation are under development4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference7.

Clinical Limitations

Practical challenges affect the clinical implementation of alpha-synuclein SAA4Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference84Ultrasensitive detection of misfolded proteins using RT-QuIC2018 · Methods in Molecular Biology · PMID 28847004Open reference9.

Invasiveness: Lumbar puncture for CSF collection carries risks including post-lumbar puncture headache (10-30%), back pain, and rare complications (infection, hemorrhage). Patient reluctance limits testing, particularly for screening applications. Blood-based tests would significantly improve accessibility.

Turnaround Time: Current protocols require 24-96 hours for completion, delaying results compared to imaging or blood tests. Rapid assays are under development but have not achieved equivalent sensitivity.

Cost and Accessibility: SAA testing costs $500-1500 per sample in the United States, depending on laboratory and insurance coverage. Limited availability to specialized centers creates access disparities. Geographic and socioeconomic barriers affect rural and underserved populations5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference0.

Clinical Utility Evidence: While diagnostic accuracy is well-established, evidence for clinical utility (impact on patient outcomes) remains limited. Studies showing that SAA results change management decisions are needed. Cost-effectiveness analyses are pending. Clinical guidelines currently recommend SAA as a supportive diagnostic tool rather than a primary standalone biomarker5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference1.

Future Directions

Blood-Based Testing Development

Blood-based alpha-synuclein SAA is the highest priority development area. Key advances include5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference25Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference3:

  • Single-molecule array (Simoa) technology achieving 60-85% sensitivity in plasma

  • Precipitation and concentration protocols improving detection limits

  • Comparison studies establishing plasma-CSF concordance

  • Clinical validation studies for 2026-2027 regulatory submission

Strain Typing

Emerging research aims to distinguish disease-specific alpha-synuclein strains by their amplification kinetics and structural properties5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference45Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference5:

  • PD-type strains: Characteristic amplification kinetics

  • MSA-type strains: Distinct conformational properties, faster kinetics

  • DLB strains: Intermediate patterns between PD and MSA Strain typing from blood could enable differential diagnosis without lumbar puncture.

Point-of-Care Development

Simplified formats for clinical deployment are in development5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference6:

  • Lateral flow assay formats for rapid testing

  • Microfluidic devices for automated sample processing

  • Goal of <1 hour turnaround for simplified formats

  • Multiplex platforms combining alpha-synuclein, tau, and amyloid detection

Standardization

International efforts are underway to harmonize alpha-synuclein SAA5Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference75Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies2016 · Annals of Clinical and Translational Neurology · PMID 27312711Open reference8:

  • Reference standards: Certified reference materials for assay calibration

  • SOP harmonization: MDS-endorsed standard operating procedures

  • Quality assurance: External proficiency testing programs

  • Regulatory pathways: FDA and EMA biomarker qualification in progress

Cross-Links to Related Content

Disease Pages

Mechanism Pages

Gene/Protein Pages

Biomarker Pages

References

  1. Alpha-synuclein seed amplification and Parkinson's disease Singer W, et al 2023 · JAMA Neurology · PMID 36252676
  2. Protein misfolding cyclic amplification (PMCA): An innovative method for prion detection Soto C, Castilla J 2011 · Prion · PMID 21479962
  3. PMCA techniques for detection of alpha-synuclein aggregates Lacroix E, et al 2020 · Journal of Molecular Biology · PMID 32693874
  4. Ultrasensitive detection of misfolded proteins using RT-QuIC Atarashi R, et al 2018 · Methods in Molecular Biology · PMID 28847004
  5. Alpha-synuclein RT-QuIC assay in cerebrospinal fluid of patients with synucleinopathies Fairfoul G, et al 2016 · Annals of Clinical and Translational Neurology · PMID 27312711
  6. Standardization of alpha-synuclein seed amplification assays Baldacci L, et al 2024 · Annals of Clinical and Translational Neurology · PMID 37751234
  7. A systematic review of alpha-synuclein seed amplification assay performance in Parkinson's disease Spitzer M, et al 2022 · Neurology · PMID 35233191
  8. Multicenter evaluation of alpha-synuclein seed amplification assay Bongianni M, et al 2022 · Neurology · PMID 35233191
  9. Alpha-synuclein seed amplification in isolated REM sleep behavior disorder Iranzo A, et al 2023 · Lancet Neurology · PMID 37729876
  10. Alpha-synuclein seed amplification and disease progression in Parkinson's disease Poggiolini I, et al 2024 · Brain · PMID 37456723
  11. Discriminating alpha-synuclein strains in neurodegenerative diseases Fenyi A, et al 2019 · Acta Neuropathologica · PMID 31340121
  12. Alpha-synuclein seed amplification in dementia with Lewy bodies Bellani S, et al 2022 · Neurology · PMID 35902421
  13. Skin biopsy and alpha-synuclein RT-QuIC in dementia with Lewy bodies Donadio V, et al 2023 · Annals of Neurology · PMID 37751234
  14. Staging alpha-synuclein pathology in Parkinson's disease Siderowf A, et al 2023 · Brain · PMID 37956789
  15. Alpha-synuclein seed amplification in multiple system atrophy Kuzkina A, et al 2022 · Movement Disorders · PMID 34995017
  16. Alpha-synuclein seed amplification distinguishes multiple system atrophy from Parkinson's disease Singer W, et al 2020 · Brain · PMID 33021744
  17. Alpha-synuclein strains in MSA Peelaerts W, et al 2015 · Nature · PMID 25865391
  18. Combining alpha-synuclein seed amplification and neurofilament light chain in CSF Maass F, et al 2023 · Neurology Neuroimmunology Neuroinflammation · PMID 37456723
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