ArticleAnnals of neurology2025
Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease.
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Associations between olfactory dysfunction and structural MRI findings in Parkinson's disease: a systematic review.Brain imaging and behavior · 2026Pooled it
- Mapping the Silent Onset of Parkinson's Disease: Monoamine Imaging in the Era of the Race for Preclinical Intervention.Current neurology and neuroscience reports · 2026Review
- A Biological Framework for Parkinson's Disease: Advances in α-Synuclein-Centered Biomarkers and Staging.Journal of neurochemistry · 2026Review
- 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
- Seed Amplification Assays for Parkinson's Disease: A Review of α-Synuclein Assays in Body Fluids and Tissues.Journal of neurochemistry · 2026Review
- Longitudinal Study of Salivary Biomarkers in the Definition of Clinico-Molecular Progression of Parkinson's Disease.Annals of clinical and translational neurology · 2026Article
- Seed Amplification Assay for α-Synuclein: Diagnostic Applications in Synucleinopathies.International journal of molecular sciences · 2025Review
- Identifying individuals at-risk of developing Parkinson's disease using a population-based recruitment strategy: The Healthy Brain Ageing Kassel Study.NPJ Parkinson's disease · 2025Article
- Uncovering the Associations of LILRB4 Genotypes With Parkinson's Disease: From Clinical Traits to Potential Pathologies.CNS neuroscience & therapeutics · 2025Article
- Seed Amplification Assays as Powerful Tools for Detecting Peripheral Biomarkers in Prion-Like Diseases.Sub-cellular biochemistry · 2025Review
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
objectiveRemote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.
methodsThe Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in longitudinal assessments and further biomarker evaluation including cerebrospinal fluid alpha-synuclein seed amplification assay (aSynSAA).
resultsAs of January 29, 2024, 49,843 participants were sent an UPSIT and 31,293 (63%) completed it. Of UPSIT completers, 8,301 (27%) scored <15th percentile. Of 1,546 who completed DAT-SPECT, 1,060 (69%) had DAT-SPECT binding <100% expected for age and sex. Participants with an UPSIT <10th percentile (n = 1,221) had greater likelihood of low DAT-SPECT binding compared to participants with an UPSIT in the 10th to 15th percentile (odds ratio, 3.01; 95% confidence interval, 1.85-4.91). Overall, 55% (198/363) of cases with UPSIT <15th percentile and DAT-SPECT <100% had positive aSynSAA, which increased to 70% (182/260) when selecting for more severe hyposmia (UPSIT <10th percentile).
interpretationRemote screening for hyposmia and reduced DAT-SPECT binding identifies participants with a high proportion positive aSynSAA. Longitudinal data will be essential to define progression patterns in these individuals to ultimately inform recruitment into disease modification clinical trials. ANN NEUROL 2025;97:730-740.
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