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Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We investigated associations of plasma proteins with blood\u2010based amyloid\/tau\/neurodegeneration\/inflammation (A\/T\/N\/I) biomarkers for Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Plasma proteomics and clinical data from the Indiana AD Research Center (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0498) were used. Association analysis of plasma proteins with blood A\/T\/N\/I biomarkers as well as diagnosis was performed, followed by replication in an independent cohort (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a0323), network analysis, pathway enrichment, and machine learning classification to identify proteins and pathways related to AD risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We identified 35 proteins associated with AD, 20 of which were replicated in the independent cohort. We identified 150, 448, and 219 proteins associated with T\/N\/I biomarkers, respectively, revealing biomarker\u2010specific pathways. Network analysis identified two modules associated with T\/N\/I biomarkers, preserved in cerebrospinal fluid (CSF), and their enriched pathways. The classification model of proteins effectively differentiated AD (area under the curve [AUC]\u00a0=\u00a00.930).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our findings suggest dysregulated plasma proteins and pathways in AD, enhancing our understanding of molecular mechanisms and diagnostic strategies for AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Plasma proteins were identified as being associated with Alzheimer's disease (AD) and plasma biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The identified proteins were replicated in both plasma and cerebrospinal fluid (CSF) proteomics.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The identified proteins were associated with AD biomarker\u2010specific pathways.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The identified proteins improved the performance of the AD classification.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Protein network analysis identified network modules and their enriched pathways.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70579","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T09:47:49Z","timestamp":1755164869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Plasma proteomic analysis identifies proteins and pathways related to Alzheimer's risk"],"prefix":"10.1002","volume":"21","author":[{"given":"Yen\u2010Ning","family":"Huang","sequence":"first","affiliation":[{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Indiana Alzheimer's Disease Research Center Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine  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School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey A.","family":"Kuchenbecker","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"},{"name":"Center for Clinical and Translational Science Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minerva M.","family":"Carrasquillo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"},{"name":"Center for Clinical and Translational Science Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil\u00fcfer","family":"Ertekin\u2010Taner","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula J.","family":"Bice","sequence":"additional","affiliation":[{"name":"Center for Neuroimaging Department of Radiology and Imaging Sciences Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Indiana Alzheimer's Disease Research Center Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Department of Neurodegenerative Disease Queen Square Institute of Neurology University College London  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases Clear Water Bay  Hong Kong 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