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Multiplexed plasma proteomics paired with supervised machine learning offers a minimally invasive and accessible approach for differential diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Plasma from 194 participants was analyzed using the Nucleic acid Linked Immuno\u2010Sandwich Assay (NULISA) Central Nervous System 120+ plasma biomarker panel. Differentially abundant protein patterns associated with Alzheimer's disease, frontotemporal lobar degeneration, Lewy body disease, and vascular disease were identified. These features were used to train supervised XGBoost classifier models. Models were then applied to participants with mild cognitive impairment (MCI) to generate data\u2010driven predictions of etiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>NULISA plasma biomarkers revealed disease\u2010specific protein patterns. XGBoost classifiers differentiated disease etiologies with high specificity. Application of the models to participants with MCI yielded robust etiologic predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results support the feasibility of using multiplexed NULISA plasma proteomics, combined with machine learning, for differential diagnosis of complex neurodegenerative dementia etiologies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71603","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:39:57Z","timestamp":1782272397000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dementia etiology classification using NULISA plasma biomarkers and machine learning"],"prefix":"10.1002","volume":"22","author":[{"given":"Kelly N.","family":"DuBois","sequence":"first","affiliation":[{"name":"Department of Translational Science and Molecular Medicine, College of Human Medicine Michigan State University  Grand Rapids Michigan USA"},{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhamoy","family":"Pal","sequence":"additional","affiliation":[{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Cook","family":"Maher","sequence":"additional","affiliation":[{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Psychiatry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Heidebrink","sequence":"additional","affiliation":[{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Neurology University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Persad","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Giordani","sequence":"additional","affiliation":[{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Department of Psychiatry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M.","family":"Hampstead","sequence":"additional","affiliation":[{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Research Program on Cognition and Neuromodulation Based Interventions (RP\u2010CNBI), Department of Psychiatry &amp; Neurology University of Michigan  Ann Arbor Michigan USA"},{"name":"Neuropsychology Section, Mental Health Service VA Ann Arbor Healthcare System  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Bakulski","sequence":"additional","affiliation":[{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Translational Science and Molecular Medicine, College of Human Medicine Michigan State University  Grand Rapids Michigan USA"},{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Neuroscience Program Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4362-2593","authenticated-orcid":false,"given":"Nicholas M.","family":"Kanaan","sequence":"additional","affiliation":[{"name":"Department of Translational Science and Molecular Medicine, College of Human Medicine Michigan State University  Grand Rapids Michigan USA"},{"name":"Michigan Alzheimer's Disease Research Center University of Michigan  Ann Arbor Michigan USA"},{"name":"Neuroscience Program Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2018.00181"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101789.2005.00605.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002093\u2010200210000\u201000001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001911\u20103"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010025\u201000872\u20107"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.96"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13859"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa286"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013211"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14442"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105322"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042834\u2010x"},{"key":"e_1_2_8_16_1","unstructured":"NULISAseq | CNS Disease Panel.Alamar Biosciences website. 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