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One subtype, enriched in African Americans and males, showed low CSF tau, elevated plasma proteins, and reduced synaptic proteins, features consistent with blood\u2013brain barrier (BBB) dysfunction. This subtype also showed the highest levels of thrombin activity, capable of cleaving tau. Introducing plasma into CSF\n                      <jats:italic>ex vivo<\/jats:italic>\n                      recapitulated the BBB subtype signature, supporting a causal role for plasma proteases in tau and synaptic protein depletion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>These findings link BBB dysfunction and plasma proteases to CSF tau loss and highlight the need for diversity in AD\u2010biomarker research.<\/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>Race and sex correlate with key AD proteomic network modules.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We identify six proteomic subtypes with distinct demographic and AD biomarker profiles.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Subtype 3 demonstrates an A+\/T\u2212 phenotype and a profile suggestive of BBB dysfunction.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Low CSF tau and neuronal proteins may stem from infiltrating plasma protease cleavage.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma spike\u2010in experiments show decreased endogenous CSF tau and neuronal proteins.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70830","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T10:45:29Z","timestamp":1762166729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomic subtyping of Alzheimer's disease CSF links blood\u2013brain barrier dysfunction to reduced levels of tau and synaptic biomarkers"],"prefix":"10.1002","volume":"21","author":[{"given":"Madison C.","family":"Bangs","sequence":"first","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshna","family":"Gadhavi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Kathleen","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duc M.","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric B.","family":"Dammer","sequence":"additional","affiliation":[{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anantharaman","family":"Shantaraman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine Emory University  Atlanta Georgia USA"},{"name":"Center for Neurodegenerative Disease Center Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C. 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