ArticleMovement disorders : official journal of the Movement Disorder Society2021
α-Synuclein Spread from Olfactory Bulb Causes Hyposmia, Anxiety, and Memory Loss in BAC-SNCA Mice.
Article in Movement disorders : official journal of the Movement Disorder Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Brain-first and body-first subtypes of Lewy body disease.Nature reviews. Neurology · 2026Review
- Time vortex: the circadian-dopaminergic dialogue in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Perampanel Blocks Transsynaptic α-Synuclein Propagation and Neurodegeneration in a Mouse Model of Lewy Body Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Olfactory sensory map is perturbed in a human wild-type α-synuclein overexpressing transgenic mouse model of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Uncovering the role of c-Fos in the bidirectional relationship between depression/anxiety behaviors and α-synuclein propagation in Parkinson's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Olfactory Dysfunction as a Window Into the Heterogeneity of Parkinson Disease.European journal of neurology · 2025Article
- Impact of α-synuclein fibril structure on seeding activity in experimental models of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Imaging advances to detect non-motor prodromal markers of Parkinson's disease and explore therapeutic translation opportunities.NPJ Parkinson's disease · 2025Review
- α-Synuclein Pathology in Synucleinopathies: Mechanisms, Biomarkers, and Therapeutic Challenges.International journal of molecular sciences · 2025Review
- 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
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice.NPJ Parkinson's disease · 2024Article
- Review
- Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Experimental Animal Models of Prodromal Parkinson's Disease.Journal of Parkinson's disease · 2024Review
- Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.Journal of Parkinson's disease · 2024Article
- Brain olfactory-related atrophy in isolated rapid eye movement sleep behavior disorder.Annals of clinical and translational neurology · 2023Article
- Mutational spectrum and clinical features of GBA1 variants in a Chinese cohort with Parkinson's disease.NPJ Parkinson's disease · 2023Article
- An optimized Nurr1 agonist provides disease-modifying effects in Parkinson's disease models.Nature communications · 2023Article
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9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundPatients with Parkinson's disease (PD) show motor symptoms as well as various non-motor symptoms. Postmortem studies of PD have suggested that initial alpha-synuclein (α-Syn) pathology develops independently in the olfactory bulb and lower brainstem, spreading from there stereotypically. However, it remains unclear how these two pathological pathways contribute to the clinicopathological progression of PD.
objectiveThe objective of this study was to examine the clinicopathological contribution of α-Syn spread from the olfactory bulb.
methodsWe conducted pathological and behavioral analyses of human α-Syn bacterial artificial chromosome transgenic mice injected with α-Syn preformed fibrils into the bilateral olfactory bulb up to 10 months postinjection.
resultsα-Syn preformed fibril injections induced more widespread α-Syn pathology in the transgenic mice than that in wild-type mice. Severe α-Syn pathology in the transgenic mice injected with α-Syn preformed fibrils was initially observed along the olfactory pathway and later in the brain regions that are included in the limbic system and have connections with it. The α-Syn pathology was accompanied by regional atrophy, neuron loss, reactive astrogliosis, and microglial activation, which were remarkable in the hippocampus. Behavioral analyses revealed hyposmia, followed by anxiety-like behavior and memory impairment, but not motor dysfunction, depression-like behavior, or circadian rhythm disturbance.
conclusionOur data suggest that α-Syn spread from the olfactory bulb mainly affects the olfactory pathway and limbic system as well as its related regions, leading to the development of hyposmia, anxiety, and memory loss in PD. © 2021 International Parkinson and Movement Disorder Society.
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