ArticleMovement disorders : official journal of the Movement Disorder Society2026
Discordance of Dopaminergic Dysfunction and Subcortical Atrophy by α-Synuclein Status in Sporadic and Genetic Parkinson's Disease.
Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- What Does α-Syn-SAA-Negative Parkinson's Disease Reveal About the Proposed "Biological Definition" of Parkinson's Disease?Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neurodegenerative pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Alpha-Synuclein in Neurodegeneration: From Shared Biology to Disease-Specific Phenotypes.Cells · 2026Review
- Postmortem brain MRI reveals differential associations of subcortical and limbic volumes with cortical thinning and neuropathology patterns.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
backgroundParkinson's disease (PD) is characterized by predominantly neuronal α-synuclein pathology and dopaminergic dysfunction. Cerebrospinal fluid (CSF) seeding amplification assays (SAA) detect α-synuclein aggregates in vivo, but not all patients with PD have a positive SAA. This pathological heterogeneity among patients may not be entirely captured by binary results from α-synuclein SAA positivity (S+) versus negativity (S-). To further dissect this biological variability, we explored spatial neuroimaging differences in S+ versus S- patients.
objectiveThe study aim was to investigate how SAA status influences imaging measures of dopamine denervation and atrophy.
methodsWe compare SAA status with CSF proteinopathy markers,
resultsBetween 64% and 95% of participants in these groups have S+ status. For all groups, S+ participants have decreased putamen DAT neurotransmission compared to S- participants, whereas S- participants have reduced MRI volume in basal ganglia structures relative to S+ participants. With striatal DAT/MRI ratios, S+ participants have disproportionately lower putamen DAT uptake relative to atrophy. In exploratory analyses, participants with cognitive impairment or hyposmia are associated with worse DAT/MRI discordance. By CSF markers, S- participants with sporadic PD have higher CSF pTau
conclusionsS+ patients exhibit more dopaminergic deficit, whereas S- patients have more subcortical atrophy across sporadic and genetic PD. Together, our findings reveal structure/function and DAT/MRI discordance, providing insight into biomarkers and pathophysiology of synucleinopathy and PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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