{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:12:06Z","timestamp":1788671526250,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 is the strongest common genetic risk factor for Alzheimer's disease (AD), yet many carriers remain cognitively unimpaired into late life. We tested whether protected \u03b54\u2010first plasma proteomics could identify proteins associated with delayed clinical onset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed harmonized Global Neurodegeneration Proteomics Consortium (GNPC) plasma proteomics. Protected \u03b54 carriers (\u03b53\/\u03b54 \u226575 years; \u03b54\/\u03b54 \u226565 years; Clinical Dementia Rating [CDR] score\u00a0=\u00a00;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0456) were compared with \u03b54 carriers with AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01096). Protein\u2010wise models adjusted for age, sex, \u03b54 dosage, and plasma proteomic principal components. Top signals were integrated with loss\u2010of\u2010function burden testing and plasma\/cerebrospinal fluid Mendelian randomization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Protected \u03b54 status was associated with 721 protein measures. Integrated analyses prioritized LILRA5, DBI, BPNT1, PTEN, EPHA1, and PCDH10 as \u03b54\u2010modified candidates and OMG, SELENOW, VAT1, and TPPP3 as broader AD\u2010related signals. TREM2 and ACE were also identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This strategy highlights immune, synaptic, metabolic\u2010stress, and myelin\/axonal pathways that may delay AD onset.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71688","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:00:06Z","timestamp":1786618806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomic signatures of protected\n                    <i>APOE<\/i>\n                    \u03b54 carriers reveal causal pathways associated with delayed Alzheimer's disease onset"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-8364","authenticated-orcid":false,"given":"Yann","family":"Le 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