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Polygenic risk scores (PRS) may therefore improve diagnostic classification.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We assessed diagnostic classification using AD\u2010PRS excluding\n APOE<\/jats:italic>\n (AD\u2010PRS\n no<\/jats:sub>\n \n APOE<\/jats:sub>\n <\/jats:italic>\n ),\n APOE<\/jats:italic>\n risk score (\n APOE<\/jats:italic>\n \u2010RS), and plasma phosphorylated tau 181 (p\u2010tau181), in 83 participants with LBD, 27 with positron emission tomography amyloid beta (A\u03b2)positive mild cognitive impairment or AD (MCI+\/AD), and 57 controls.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Together AD\u2010PRS\n no<\/jats:sub>\n \n APOE<\/jats:sub>\n <\/jats:italic>\n and\n APOE<\/jats:italic>\n \u2010RS performed similarly to p\u2010tau181 in discriminating MCI+\/AD from controls (area under the curve 76% vs. 79%) and LBD (71% vs. 72%). In LBD, A\u03b2 positivity was significantly associated with\n APOE\u2010<\/jats:italic>\n RS, but not with AD\u2010PRS\n no<\/jats:sub>\n \n APOE<\/jats:sub>\n <\/jats:italic>\n , or p\u2010tau181. Combining AD\u2010PRS\n no<\/jats:sub>\n \n APOE<\/jats:sub>\n <\/jats:italic>\n ,\n APOE\u2010<\/jats:italic>\n RS, and p\u2010tau181 improved the\u00a0discrimination of MCI+\/AD from controls (81%) and LBD (75%), and the\u00a0detection of A\u03b2 in LBD (82%).\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n A\u03b2 deposition in LBD was associated with\n APOE<\/jats:italic>\n , while MCI+\/AD was also associated with AD\u2010PRS beyond\n APOE<\/jats:italic>\n . AD\u2010PRS explains phenotypic variance not captured by\n APOE<\/jats:italic>\n or p\u2010tau181.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n We investigated Alzheimer's disease (AD) polygenic risk score (PRS), apolipoprotein E (\n APOE<\/jats:italic>\n ), and plasma phosphorylated tau 181 (p\u2010tau181) to classify AD and Lewy body dementia (LBD).\n <\/jats:p>\n <\/jats:list-item>\n \n \n AD\u2010PRS with\n APOE<\/jats:italic>\n achieved similar classification accuracy to p\u2010tau181.\n <\/jats:p>\n <\/jats:list-item>\n \n \n AD\u2010PRS without\n APOE<\/jats:italic>\n significantly contributed to discriminating AD from LBD.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Amyloid beta positivity in LBD was associated with\n APOE<\/jats:italic>\n but not AD\u2010PRS without\n APOE<\/jats:italic>\n or p\u2010tau181.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Combining AD\u2010PRS,\n APOE<\/jats:italic>\n , and p\u2010tau181 improved diagnostic classification accuracy.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.14381","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T04:09:53Z","timestamp":1737691793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Polygenic risk discriminates Lewy body dementia from Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Anna","family":"McKeever","sequence":"first","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK"},{"name":"Cambridgeshire and Peterborough NHS Foundation Trust Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Swann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Malpetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK"},{"name":"Cambridge University Hospitals NHS Foundation Trust Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Donaghy","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Thomas","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry H. 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