ArticleScience advances2020
Determinants of seeding and spreading of α-synuclein pathology in the brain.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 105 citations in OpenAlex.
- Selective Neuronal Vulnerability to Alpha-Synuclein Pathology in Parkinson's Disease: A Critical Review of Mechanistic Rationale and Biomarker Stratification.Medical sciences (Basel, Switzerland) · 2026Review
- Selective vulnerability of monoaminergic neurons and network spread of alpha-synuclein jointly explain pathology progression in Parkinson's disease models.Neurobiology of disease · 2026Article
- Selective molecular and network architecture features underlie brain cortical atrophy in dementia with Lewy bodies.Journal of biomedical science · 2026Article
- Myelin damage in donor skin differentiates between synucleinopathies.NPJ Parkinson's disease · 2026Article
- Sex-specific effects of exercise on motor coordination and extended basal ganglia physiology.bioRxiv : the preprint server for biology · 2026Article
- Activity-Dependent Regulation of Basal Forebrain Cholinergic Neurons by Striatal Spiny Projection Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Rise-and-fall dynamics reveal a molecular and cellular vulnerability axis in prion-likebioRxiv : the preprint server for biology · 2026Article
- Mapping cellular vulnerability in Parkinson's disease using retro-AAVs and preformed α-synuclein fibrils.Translational neurodegeneration · 2026Article
- Discovery of Abundant Nano-scale Lymphatic-like Vessels in Brains.bioRxiv : the preprint server for biology · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Functional Magnetic Resonance Imaging (fMRI) Signatures of Progression and Phenoconversion in Prodromal Synucleinopathies.Movement disorders : official journal of the Movement Disorder Society · 2025Article
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- Development of convolutional neural networks for automated brain-wide histopathological analysis in mouse models of synucleinopathies.NPJ Parkinson's disease · 2025Article
- Evaluating alpha-synuclein proteinopathy and consequences for birdsong in zebra finch basal ganglia area X.Behavioural brain research · 2025Article
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- Alpha-synuclein pathology and Parkinson's disease-related olfactory dysfunctions: an update on preclinical models and therapeutic approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.Molecular neurodegeneration · 2025Review
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- Rotenone accelerates endogenous α-synuclein spreading and enhances neurodegeneration in an intra-striatal α-synuclein preformed fibril injected mouse model of Parkinson's disease.Frontiers in cellular neuroscience · 2025Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
In Parkinson's disease (PD), fibrillar forms of α-synuclein are hypothesized to propagate through synaptically coupled networks, causing Lewy pathology (LP) and neurodegeneration. To more rigorously characterize the determinants of spreading, preformed α-synuclein fibrils were injected into the mouse pedunculopontine nucleus (PPN), a brain region that manifests LP in PD patients and the distribution of developing α-synuclein pathology compared to that ascertained by anterograde and retrograde connectomic mapping. Within the PPN, α-synuclein pathology was cell-specific, being robust in PD-vulnerable cholinergic neurons but not in neighboring noncholinergic neurons. While nearly all neurons projecting to PPN cholinergics manifested α-synuclein pathology, the kinetics, magnitude, and persistence of the propagated pathology were unrelated to the strength of those connections. Thus, neuronal phenotype governs the somatodendritic uptake of pathological α-synuclein, and while the afferent connectome restricts the subsequent spreading of pathology, its magnitude and persistence is not a strict function of the strength of coupling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.