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Apolipoprotein E \u03b54 carrier status modified sex\u2010specific alterations of multiple proteins including S100A9 and NEFL for A\u03b242 and MAPK9 and MAPKAPK2 for p\u2010tau. Male\u2010specific proteins, enriched in microglia, were involved in activating innate immune response. The male network exhibited direct connections among 30 proteins and highlighted MAPKAPK2 as a hub. Female\u2010specific proteins, enriched in endothelial cells, were involved in regulating protein metabolic process. The female network exhibited direct connections among 43 proteins and highlighted CSNK2A2 and PRKCA as hubs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings provide insights into mechanistic understanding of sex differences in AD risk.<\/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>Our proteomic study of 6162 proteins (targeted by 7006 aptamers) in cerebrospinal fluid (CSF) from 2496 participants identified and replicated 68 male\u2010specific and 116 female\u2010specific proteins associated with cerebrospinal fluid amyloid beta 42 and\/or phosphorylated tau levels.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Male\u2010specific proteins, enriched in microglia, were involved in activation of innate immune response. The male network highlighted MAPKAPK2 involved in chronic neuronal neuroinflammation as a hub.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Female\u2010specific proteins, enriched in endothelial cells, were involved in regulation of protein metabolic process and response to external stimuli. The female network highlighted PRKCA regulating synaptic plasticity and CSNK2A2 protein involved in neuroplasticity as hubs.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71063","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:03:07Z","timestamp":1767891787000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CSF proteomic profiling with amyloid and tau pathology identifies distinctive sex\u2010specific alteration of multiple proteins involved in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Anh N.","family":"Do","sequence":"first","affiliation":[{"name":"Division of Biostatistics Washington University School of Medicine  St. Louis Missouri USA"},{"name":"NeuroGenomics and Informatics Center Washington University School 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