Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease
dc.contributor.author | Brown, Ethan G. | |
dc.contributor.author | Chahine, Lana M. | |
dc.contributor.author | Siderowf, Andrew | |
dc.contributor.author | Gochanour, Caroline | |
dc.contributor.author | Kurth, Ryan | |
dc.contributor.author | Marshall, Micah J. | |
dc.contributor.author | Caspell-Garcia, Chelsea | |
dc.contributor.author | Brumm, Michael C. | |
dc.contributor.author | Stanley, Craig E., Jr. | |
dc.contributor.author | Korell, Monica | |
dc.contributor.author | McMahon, Bridget | |
dc.contributor.author | Kuhl, Maggie | |
dc.contributor.author | Fabrizio, Kimberly | |
dc.contributor.author | Heathers, Laura | |
dc.contributor.author | Concha-Marambio, Luis | |
dc.contributor.author | Soto, Claudio | |
dc.contributor.author | Chowdhury, Sohini | |
dc.contributor.author | Coffey, Christopher S. | |
dc.contributor.author | Foroud, Tatiana M. | |
dc.contributor.author | Simuni, Tanya | |
dc.contributor.author | Marek, Kenneth | |
dc.contributor.author | Tanner, Caroline M. | |
dc.contributor.author | Parkinson Progression Marker Initiative | |
dc.contributor.department | Medical and Molecular Genetics, School of Medicine | |
dc.date.accessioned | 2025-04-18T08:22:14Z | |
dc.date.available | 2025-04-18T08:22:14Z | |
dc.date.issued | 2025 | |
dc.description.abstract | Objective: 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. Methods: 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). Results: 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). Interpretation: 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. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Brown EG, Chahine LM, Siderowf A, et al. Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease. Ann Neurol. 2025;97(4):730-740. doi:10.1002/ana.27158 | |
dc.identifier.uri | https://hdl.handle.net/1805/47152 | |
dc.language.iso | en_US | |
dc.publisher | Wiley | |
dc.relation.isversionof | 10.1002/ana.27158 | |
dc.relation.journal | Annals of Neurology | |
dc.rights | Attribution-NonCommercial 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | PMC | |
dc.subject | Parkinson disease | |
dc.subject | Dopamine plasma membrane transport proteins | |
dc.subject | Synucleinopathies | |
dc.subject | Olfaction disorders | |
dc.title | Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha-Synuclein Disease | |
dc.type | Article |