{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:34:21Z","timestamp":1784921661303,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG066515"],"award-info":[{"award-number":["AG066515"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K99AG071837"],"award-info":[{"award-number":["K99AG071837"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS062684"],"award-info":[{"award-number":["NS062684"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS075097"],"award-info":[{"award-number":["NS075097"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS115114"],"award-info":[{"award-number":["NS115114"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARFD\u201021\u2010849349"],"award-info":[{"award-number":["AARFD\u201021\u2010849349"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>More than half of neurodegenerative disease patients have multiple pathologies at autopsy; however, most receive one diagnosis during life. We used the \u03b1\u2010synuclein seed amplification assay (\u03b1Syn\u2010SAA) and CSF biomarkers for amyloidosis and Alzheimer's disease (AD) neuropathological change (ADNC) to determine the frequency of co\u2010pathologies in participants clinically diagnosed with Lewy body (LB) disease or AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using receiver operating characteristic analyses on retrospective CSF samples from 150 participants determined \u03b1Syn\u2010SAA accuracy, sensitivity, and specificity for identifying clinically defined LB disease and predicting future change in clinical diagnosis. CSF biomarkers helped determine the frequency of concomitant Lewy body pathology, ADNC, and\/or amyloidosis in participants with LB disease and AD, across clinical spectra.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following a decade\u2010long follow\u2010up, the clinically or autopsy\u2010defined diagnosis changed for nine participants. \u03b1Syn\u2010SAA demonstrated improved accuracy (91.3%), sensitivity (89.3%), and specificity (93.3%) for identifying LB disease compared to all non\u2010LB disease, highlighting the limitations of clinical diagnosis alone. When examining biomarkers of co\u2010pathology, amyloidosis was present in 18%, 48%, and 71% (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>(2)\u2009=\u200913.56, <jats:italic>p<\/jats:italic>\u2009=\u20090.001) and AD biomarkers were present in 0%, 8.7%, and 42.9% (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>(2)\u2009=\u200918.44, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) of LB disease participants with different stages of cognitive impairment respectively. Co\u2010occurring biomarkers for \u03b1Syn\u2010SAA and amyloidosis were present in 12% and 14% of AD compared to 43% and 57% LB disease participants with different stages of cognitive impairment (<jats:italic>\u03c7<\/jats:italic><jats:sup>2<\/jats:sup>(3)\u2009=\u200913.87, <jats:italic>p<\/jats:italic>\u2009=\u20090.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our study shows that using a combination of \u03b1Syn\u2010SAA and AD biomarkers can identify people with \u03b1Syn, ADNC, and co\u2010pathology better and earlier than traditional clinical diagnostic criteria alone.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52034","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T10:36:30Z","timestamp":1709548590000},"page":"1197-1210","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Multiple biomarkers improve diagnostic accuracy across Lewy body and Alzheimer's disease spectra"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2011-7882","authenticated-orcid":false,"given":"Melanie J.","family":"Plastini","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Abdelnour","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina B.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0640-5247","authenticated-orcid":false,"given":"Edward N.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-3238","authenticated-orcid":false,"given":"Marian","family":"Shahid\u2010Besanti","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lamoureux","sequence":"additional","affiliation":[{"name":"Amprion Clinical Laboratory  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin I.","family":"Andreasson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"},{"name":"Chan Zuckerberg Biohub  San Francisco California 94158 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey A.","family":"Kerchner","sequence":"additional","affiliation":[{"name":"Pharma Research and Early Development, F. Hoffmann\u2010La Roche, Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Montine","sequence":"additional","affiliation":[{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"},{"name":"Department of Pathology Stanford University School of Medicine  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"},{"name":"Department of Epidemiology and Population Health Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3424-7143","authenticated-orcid":false,"given":"Kathleen L.","family":"Poston","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"},{"name":"Knight Initiative for Brain Resilience Stanford University  Stanford California USA"},{"name":"Wu Tsai Neurosciences Institute Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa438"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102019\u2010321111"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750\u20103639.2000.tb00269.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(16)30291\u20105"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy146"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.01.017"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004567"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010201187"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.0606"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010150606"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.23.2215"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002449\u20107"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab431"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200878"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010021\u201001175\u2010w"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2020.1731306"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29284"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(23)00109\u20106"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010020\u201002160\u20108"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002450\u20100"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD\u2010225111"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00405-2"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318191c7dd"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27575"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.06.048"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24893"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.09.004"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.02.023"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.6.745"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3233\/jpd\u2010130189"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009323"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000004058"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102796.2004.01388.x"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27802"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010011\u20100910\u20103"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010007\u20100237\u20102"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750\u20103639.2007.00117.x"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/15622975.2017.1375556"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa021"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010023\u201011810\u20102"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50897"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26453"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100390"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26668"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2020.102333"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010021\u201000946\u2010w"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12294"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13109"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001834"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010022\u201001388\u20107"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.52034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T16:42:43Z","timestamp":1715704963000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.52034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":54,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/acn3.52034"],"URL":"https:\/\/doi.org\/10.1002\/acn3.52034","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"value":"2328-9503","type":"print"},{"value":"2328-9503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,4]]},"assertion":[{"value":"2023-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}