ArticleMovement disorders : official journal of the Movement Disorder Society2026
Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha-Synuclein Seed Amplification Assay.
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 9 papers.
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9 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
- Methodological Challenges in Interpreting SAA-Defined Imaging Subgroups in Parkinson's Disease.Annals of neurology · 2026Article
- Reply to "Methodological Challenges in Interpreting SAA-Defined Imaging Subgroups in Parkinson's Disease".Annals of neurology · 2026Article
- Reply to: "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
- Effects of α-synuclein pathology on synaptic dysfunction and clinical outcomes in normal aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic Associations of Parkinson's Disease Clinical, Pathological, and Data-Driven Subtypes.Genes · 2026Article
- Timing of device-aided therapy initiation in Parkinson's disease: reference estimates for healthcare planning and biological heterogeneity.Clinical parkinsonism & related disorders · 2026Article
- 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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Abstract
backgroundThe cerebrospinal fluid alpha-synuclein seed amplification assay (CSFasynSAA) detects alpha-synuclein aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA remain undefined.
objectivesDescribe clinical and neuroimaging characteristics of CSFasynSAA-negative sPD individuals in the Parkinson's Progression Markers Initiative (PPMI).
methodsWe identified sPD PPMI participants with a negative CSFasynSAA (SAA-, n = 80) or positive CSFasynSAA (SAA+, n = 856) result at baseline. For comparative analysis between groups, we used a reduced dataset (n = 79 SAA- and n = 237 SAA+) propensity-score matched on age, sex, and time since clinical diagnosis. Clinical parameters, dopamine transporter-single photon emission computed tomography (DAT-SPECT), and magnetic resonance imaging (MRI) brain volumetrics were analyzed.
resultsThe SAA- and matched SAA+ groups had similar motor performance on the Movement Disorder Society Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) and similar cognitive performance on the Montreal Cognitive Assessment (MoCA) at baseline. The proportion with severe hyposmia was 12% for SAA- versus 73% for SAA+ (P < 0.001). Per PPMI enrollment criteria all participants were classified as having an abnormal DAT-SPECT. There were no significant differences in median quantitative DAT-SPECT measures between groups. The SAA- group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, 14.3% of SAA- participants had a change in diagnosis versus 0.9% of SAA+ participants.
conclusionsAt baseline, SAA- sPD PPMI participants have a substantially lower rate of hyposmia, but otherwise cannot be readily distinguished from SAA+ participants based on clinical characteristics. However, SAA- participants have a greater degree of subcortical brain atrophy, and approximately one out of seven SAA- participants received a change in diagnosis. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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