{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:35:08Z","timestamp":1780914908922,"version":"3.54.1"},"posted":{"date-parts":[[2026,2,6]]},"group-title":"Bioinformatics","reference-count":15,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Understanding of early Alzheimer progression is critical for timely diagnosis and treatment evaluation, but traditional diagnostic groups often lack sensitivity to subtle early-stage changes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We developed SLOPE, an unsupervised dimensionality reduction method that models the amyloid progression in AD on a continuous scale which preserves the temporal sequence of follow-up visits. Applied to longitudinal amyloid PET data, SLOPE generated a two-dimensional trajectory capturing global amyloid accumulation across the AD continuum.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>SLOPE-derived pseudotime scores better preserved temporal consistency across diagnostic groups and longitudinal follow-up visits and can be generalized to held-out subjects. The learned trajectory revealed biologically consistent amyloid spreading patterns and greater sensitivity to early progression than global amyloid SUVR.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>SLOPE provides a continuous staging of amyloid pathology that complements global amyloid measures by capturing early localized progression.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.03.703568","type":"posted-content","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T19:15:18Z","timestamp":1770405318000},"source":"Crossref","is-referenced-by-count":1,"title":["Learning a Continuous Progression Trajectory of Amyloid in Alzheimer disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-6213","authenticated-orcid":false,"given":"Mingzhao","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Computer Science, Indiana University Indianapolis, Indianapolis, IN, 46202, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-0279","authenticated-orcid":false,"given":"Fahad","family":"Mehfooz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Informatics, Indiana University Indianapolis, Indianapolis, IN, 46202, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of California Los Angeles 404 Westwood Plaza Engineering IV, Los Angeles, CA, 90095, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yipei","family":"Wang","sequence":"additional","affiliation":[{"name":"Elmore Family School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, 47906, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8277-5202","authenticated-orcid":false,"given":"Shiaofen","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Informatics, Indiana University Indianapolis, Indianapolis, IN, 46202, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1376-8532","authenticated-orcid":false,"given":"Andrew J.","family":"Saykin","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, 46202, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Elmore Family School of Electrical and Computer Engineering, Purdue University, West Lafayette, IN, 47906, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Informatics, Indiana University Indianapolis, Indianapolis, IN, 46202, U.S."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"5","key":"2026022300550897000_2026.02.03.703568v2.1","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/ana.21509","article-title":"Prodromal Alzheimer\u2019s disease: successive emergence of the clinical symptoms","volume":"64","year":"2008","journal-title":"Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society"},{"key":"2026022300550897000_2026.02.03.703568v2.2","doi-asserted-by":"crossref","unstructured":"Brockmann R , Nixon J , Love BL , Yunusa I. Impacts of FDA approval and Medicare restriction on antiamyloid therapies for Alzheimer\u2019s disease: patient outcomes, healthcare costs, and drug development. 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Multi-modal Imaging-based Pseudotime Analysis of Alzheimer progression. In: Biocomputing 2025: Proceedings of the Pacific Symposium. 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