{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:10:34Z","timestamp":1788862234112,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["MJFF\u2010022651"],"award-info":[{"award-number":["MJFF\u2010022651"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha\u2010synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single\u2010photon emission computed tomography imaging (DAT\u2010SPECT) and alpha\u2010synuclein aggregation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60\u2010years 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\u2010SPECT, which determined eligibility for enrollment in longitudinal assessments and further biomarker evaluation including cerebrospinal fluid alpha\u2010synuclein seed amplification assay (aSynSAA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 &lt;15th percentile. Of 1,546 who completed DAT\u2010SPECT, 1,060 (69%) had DAT\u2010SPECT binding &lt;100% expected for age and sex. Participants with an UPSIT &lt;10th percentile (n\u2009=\u20091,221) had greater likelihood of low DAT\u2010SPECT binding compared to participants with an UPSIT in the 10th to 15th percentile (odds ratio, 3.01; 95% confidence interval, 1.85\u20134.91). Overall, 55% (198\/363) of cases with UPSIT &lt;15th percentile and DAT\u2010SPECT &lt;100% had positive aSynSAA, which increased to 70% (182\/260) when selecting for more severe hyposmia (UPSIT &lt;10th percentile).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Remote screening for hyposmia and reduced DAT\u2010SPECT 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\u2013740<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27158","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T01:44:26Z","timestamp":1735091066000},"page":"730-740","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Staged Screening Identifies People with Biomarkers Related to Neuronal Alpha\u2010Synuclein Disease"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9744-8562","authenticated-orcid":false,"given":"Ethan G.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana M.","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Perelman School of Medicine  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Gochanour","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Kurth","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah J.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Caspell\u2010Garcia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Brumm","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Craig E.","family":"Stanley","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Korell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weill Institute for Neurosciences University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"McMahon","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Kuhl","sequence":"additional","affiliation":[{"name":"The Michael J. 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