ArticleNPJ Parkinson's disease2025
Backtracking α-synuclein pathology: social deficits precede motor symptoms in Parkinson's disease.
Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Soluble α-synuclein oligomers drive transient corticostriatal pathology and delayed nigral vulnerability in a mouse model of early α-synucleinopathy.Acta neuropathologica communications · 2026Article
- Dopamine-endocannabinoid crosstalk drives exercise-induced bidirectional plasticity in Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Predictive factors of global cognitive impairment in de novo Parkinson disease with normal cognition at baseline: a 10-year cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
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Authors and funding
10 authors.
Funding
Abstract
In Parkinson's disease (PD), degeneration of dopaminergic neurons in the substantia nigra pars compacta and accumulation of alpha-synuclein (α-syn) aggregates are linked to motor impairments. However, up to 80% of PD patients also experience cognitive and psychiatric issues. The effects of α-syn aggregates on limbic structures involved in social behavior are less studied. Here, we hypothesize that early synaptic changes in the mesolimbic dopaminergic system occur before motor symptoms, affecting social cognition (SC). Four weeks after intrastriatal injections of human-α-syn pre-formed fibrils, at a pre-motor stage, dorsolateral striatum plasticity remains intact, while long-term potentiation in the Nucleus Accumbens (NAc)-Core is lost, correlating with deficits in SC and spatial memory. Reduced dopaminergic and glutamatergic inputs and decreased dendritic spine density were also observed. Sub-chronic L-Dopa treatment reversed these changes. Our data suggest that SC is affected early in this synucleinopathy, with synaptic alterations in the NAc-Core playing a key role.
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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 Socratic graph.