Journal article
Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease
Annals of neurology, Vol.97(4), pp.730-740
04/2025
DOI: 10.1002/ana.27158
PMCID: PMC11889527
PMID: 39719857
Abstract
Remote 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.
The 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).
As 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).
Remote 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 2024.
Details
- Title: Subtitle
- Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease
- Creators
- Ethan G Brown - University of California, San FranciscoLana M Chahine - University of PittsburghAndrew Siderowf - University of PennsylvaniaCaroline Gochanour - University of IowaRyan Kurth - University of IowaMicah J Marshall - University of IowaChelsea Caspell-Garcia - University of IowaMichael C Brumm - University of IowaCraig E Stanley Jr - Institute for Neurodegenerative DisordersMonica Korell - University of California, San FranciscoBridget McMahon - Institute for Neurodegenerative DisordersMaggie Kuhl - Michael J. Fox FoundationKimberly Fabrizio - Institute for Neurodegenerative DisordersLaura Heathers - Indiana University – Purdue University IndianapolisLuis Concha-Marambio - AmprionClaudio Soto - AmprionSohini Chowdhury - Michael J. Fox FoundationChristopher S Coffey - University of IowaTatiana M Foroud - Indiana University – Purdue University IndianapolisTanya Simuni - Northwestern UniversityKenneth Marek - Institute for Neurodegenerative DisordersCaroline M Tanner - University of California, San FranciscoParkinson Progression Marker Initiative
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.97(4), pp.730-740
- DOI
- 10.1002/ana.27158
- PMID
- 39719857
- PMCID
- PMC11889527
- NLM abbreviation
- Ann Neurol
- ISSN
- 1531-8249
- eISSN
- 1531-8249
- Publisher
- WILEY; HOBOKEN
- Grant note
- MJFF-022651 / Michael J. Fox Foundation for Parkinson's Research
- Language
- English
- Electronic publication date
- 12/24/2024
- Date published
- 04/2025
- Academic Unit
- Biostatistics
- Record Identifier
- 9984759888602771
Metrics
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