{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T06:00:05Z","timestamp":1785477605491,"version":"3.56.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Accurate clinical diagnosis of neurodegenerative diseases remains challenging, particularly when individuals have mixed pathologies. We implemented the generalizable protein\u2010based neurodegenerative disease artificial intelligence (GPND\u2010AI) classifier using the NUcleic acid\u2010Linked Immuno\u2010Sandwich Assay (NULISA) central nervous system (CNS) panel to classify Alzheimer's disease, Parkinson's disease, frontotemporal dementia, dementia with Lewy bodies, and healthy controls, while disentangling mixed pathologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Proteomic and clinical information from the Charles F. and Joanne Knight Alzheimer's Disease Research Center (Knight\u2010ADRC) and Movement Disorder Clinic were used to train and test the GPND\u2010AI classifier. External validation was performed in a Banner Sun Health Research Institute cohort and additional Knight\u2010ADRC samples with neuropathologically confirmed diagnoses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>GPND\u2010AI identified 15 proteins that achieve an area under the curve (AUC) of 0.955 and 92.3% accuracy across five diagnostic categories. In validation cohort, predicted co\u2010pathologies significantly correlated with clinical characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>GPND\u2010AI identified a 15\u2010protein panel that accurately classifies individuals across the four major neurodegenerative diseases. Validation against neuropathology\u2010confirmed diagnoses supports the utility of proteomics\u2010based approaches for mapping disease\u2010specific and co\u2010existing neurodegenerative processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71420","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:40:12Z","timestamp":1777434012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GPND\u2010AI NULISA: A 15\u2010Protein AI classifier for diagnosis and co\u2010pathology profiling across neurodegenerative diseases"],"prefix":"10.1002","volume":"22","author":[{"given":"Ying","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa N","family":"Denkinger","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yike","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Western","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jigyasha","family":"Timsina","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington 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S.","family":"Benzinger","sequence":"additional","affiliation":[{"name":"Department of Genetics Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Radiology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Knight Alzheimer Disease Research Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E.","family":"Schindler","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Knight Alzheimer Disease Research Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Hope Center for Neurologic Disorders Washington University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Knight Alzheimer Disease Research Center Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Holtzman","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Knight Alzheimer Disease Research Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Hope Center for Neurologic Disorders Washington University  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Perlumtter","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Radiology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Neuroscience Programs in Occupational Therapy and Physical Therapy Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Joy","family":"Snider","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan C.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Radiology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Kotzbauer","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"},{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"},{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience &amp; 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