ArticleEBioMedicine2025
Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional study.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha-Synuclein Seed Amplification Assay.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Seed Amplification Assays for Parkinson's Disease: A Review of α-Synuclein Assays in Body Fluids and Tissues.Journal of neurochemistry · 2026Review
- Prodromal Lewy Body Symptoms and α-Synuclein Seeding in Idiopathic Olfactory Dysfunction.Movement disorders clinical practice · 2026Article
- Imaging biomarkers in neurodegenerative diseases: advances and challenges.Frontiers in aging neuroscience · 2026Review
- Review
- Seed Amplification Assay for α-Synuclein: Diagnostic Applications in Synucleinopathies.International journal of molecular sciences · 2025Review
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Authors and funding
12 authors.
Funding
Abstract
backgroundSynuclein pathology in neurodegenerative diseases, such as Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur.
methodsData from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA.
findingsCSF α-syn SAA was positive in 48% (34/71) of hyposmic compared to 4% (1/25) of normosmic PARS participants (relative risk, 11.97; 95% CI, 1.73-82.95). Among α-syn SAA positive hyposmics 65% remained without a DAT deficit for up to four years follow-up. α-syn SAA positive hyposmics were at higher risk of having DAT deficit (12 of 34) compared to α-syn SAA negative hyposmics (4 of 37; relative risk, 3.26; 95% CI, 1.16-9.16), and 7 of 12 α-syn SAA positive hyposmics with DAT deficit developed symptoms consistent with synucleinopathy.
interpretationApproximately fifty percent of PARS participants with hyposmia, easily detected using simple, widely available tests, have synuclein pathology detected by α-syn SAA. Approximately, one third (12 of 34) α-syn SAA positive hyposmic individuals also demonstrate DAT deficit. This study suggests a framework to investigate screening paradigms for synuclein pathology that could lead to design of therapeutic prevention studies in individuals without symptoms.
fundingThe study was funded by the U.S. Department of Defense, the Helen Graham Foundation and the Michael J. Fox Foundation for Parkinson's Research.
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