ArticleActa neuropathologica communications2021
Association between CSF alpha-synuclein seeding activity and genetic status in Parkinson's disease and dementia with Lewy bodies.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 4 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 4 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Cerebrospinal fluid biomarkers for diagnosis of Parkinson's disease: a systematic review and network meta-analysis.Journal of neurology · 2025Pooled it
- Biomarkers in Ataxia-Telangiectasia: a Systematic Review.Journal of neurology · 2025Pooled it
- Biofluid Detection of Pathological α-Synuclein in the Prodromal Phase of Synucleinopathies.Journal of Parkinson's disease · 2024Pooled it
- Alpha-Synuclein Strain Variability in Body-First and Brain-First Synucleinopathies.Frontiers in aging neuroscience · 2022Pooled it
- Diffusion MRI and α-Synuclein Seed Amplification Status in Parkinson's Disease.Annals of neurology · 2026Article
- Complementary Mitochondrial and α-Synuclein Signatures Refine Biological Stratification of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- 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
- Reply to "Methodological Challenges in Interpreting SAA-Defined Imaging Subgroups in Parkinson's Disease".Annals of neurology · 2026Article
- Inter-assay and Inter-site Performance of Alpha-Synuclein Seed Amplification Assays in Synucleinopathies: A Multicenter 2 × 2 Protocol Comparison.Neurology and therapy · 2026Article
- Rethinking Mitochondrial Parkinson's Disease in the α-Synuclein Seed Amplification Assays Era.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Preparing for Parkinson's disease prevention trials: Current progress and future directions.Journal of Parkinson's disease · 2026Review
- CSF alpha-Synuclein Seed Amplification Assay results in routine clinically collected samples.Journal of Parkinson's disease · 2026Article
- A Systematic Comparison of Alpha-Synuclein Seed Amplification Assays for Increasing Reproducibility.Annals of clinical and translational neurology · 2026Review
- Discordance of Dopaminergic Dysfunction and Subcortical Atrophy by α-Synuclein Status in Sporadic and Genetic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Seed Amplification Assays for Parkinson's Disease: A Review of α-Synuclein Assays in Body Fluids and Tissues.Journal of neurochemistry · 2026Review
- LRRK2 and GBA1 in Lewy body diseases: neuropathological subtypes at opposite ends of a spectrum?Molecular neurodegeneration · 2026Review
- Variants in the proteasome regulator PSMF1 cause a phenotypic spectrum from parkinsonism to perinatal lethality.Nature communications · 2026Article
- Clinical correlates of a negative cerebrospinal fluid α-synuclein seed amplification assay result in Parkinson's disease.NPJ Parkinson's disease · 2026Article
- A Real Time Quaking Induced Conversion (RT-QuIC) Assay for Detection of Misfolded Insulin Protein.bioRxiv : the preprint server for biology · 2026Article
- Pathology-Anchored Transcranial Sonography: A Cascaded Super-Resolution Deep Learning System for Early-Stage Parkinson's Disease Grading.NPJ Parkinson's disease · 2026Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinicopathological heterogeneity in Lewy-body diseases (LBD) highlights the need for pathology-driven biomarkers in-vivo. Misfolded alpha-synuclein (α-Syn) is a lead candidate based on its crucial role in disease pathophysiology. Real-time quaking-induced conversion (RT-QuIC) analysis of CSF has recently shown high sensitivity and specificity for the detection of misfolded α-Syn in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this study we performed the CSF RT-QuIC assay in 236 PD and 49 DLB patients enriched for different genetic forms with mutations in GBA, parkin, PINK1, DJ1, and LRRK2. A subgroup of 100 PD patients was also analysed longitudinally. We correlated kinetic seeding parameters of RT-QuIC with genetic status and CSF protein levels of molecular pathways linked to α-Syn proteostasis. Overall, 85% of PD and 86% of DLB patients showed positive RT-QuIC α-Syn seeding activity. Seeding profiles were significantly associated with mutation status across the spectrum of genetic LBD. In PD patients, we detected positive α-Syn seeding in 93% of patients carrying severe GBA mutations, in 78% with LRRK2 mutations, in 59% carrying heterozygous mutations in recessive genes, and in none of those with bi-allelic mutations in recessive genes. Among PD patients, those with severe GBA mutations showed the highest seeding activity based on RT-QuIC kinetic parameters and the highest proportion of samples with 4 out of 4 positive replicates. In DLB patients, 100% with GBA mutations showed positive α-Syn seeding compared to 79% of wildtype DLB. Moreover, we found an association between α-Syn seeding activity and reduced CSF levels of proteins linked to α-Syn proteostasis, specifically lysosome-associated membrane glycoprotein 2 and neurosecretory protein VGF.These findings highlight the value of α-Syn seeding activity as an in-vivo marker of Lewy-body pathology and support its use for patient stratification in clinical trials targeting α-Syn.
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