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We aimed to map the proteomic correlates of cerebral amyloidosis and link them to clinical variability within A\u03b2+ individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We integrated quantitative amyloid PET with large\u2010scale plasma proteomics (\u223c7000 proteins; SomaScan version 4.1) in Knight Alzheimer's Disease Research Center and Bio\u2010Hermes cohorts (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01429). Proteome\u2010wide association analyses identified proteins associated with amyloid load, followed by unsupervised clustering and pathway enrichment analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We identified 454 amyloid\u2010associated proteins, of which 54 replicated cross\u2010cohort. A derived 54\u2010protein proteomic score correlated with amyloid burden, AD biomarkers, and clinical severity. Pathway analyses of clinically distinct protein clusters revealed coordinated enrichment of intracellular signaling, immune, and proteostasis modules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings delineate the circulating proteomic signature of cerebral amyloidosis and support plasma proteomics as a complementary approach to phosphorylated tau at threonine 217 and amyloid PET for biological stratification and characterization of disease heterogeneity in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71611","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T08:52:37Z","timestamp":1782118357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood\u2010based proteomic signature of amyloidosis: identification of novel regulators of amyloid load"],"prefix":"10.1002","volume":"22","author":[{"given":"Yike","family":"Chen","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":"Michael R.","family":"Duggan","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience National Institute on Aging  Baltimore Maryland 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":"Ying","family":"Xu","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":"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":"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":"John","family":"Budde","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":"Suzanne E.","family":"Schindler","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  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"}],"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammie L. 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