{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:49:11Z","timestamp":1793828951309,"version":"4.6.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG10124"],"award-info":[{"award-number":["AG10124"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS088341"],"award-info":[{"award-number":["NS088341"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>We analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested baseline CSF biomarkers for prediction of clinical decline in PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Amyloid\u2010\u03b2 1 to 42 (A\u03b2<jats:sub>42<\/jats:sub>), total tau (t\u2010tau) and phosphorylated tau (p\u2010tau) at the threonine 181 position were measured using the high\u2010precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3\u2009years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear\u2010mixed effects models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found patients with PD had lower CSF t\u2010tau (median = 157.7 pg\/mL; range = 80.9\u2013467.0); p\u2010tau (median = 13.4 pg\/mL; range = 8.0\u201340.1), and A\u03b2<jats:sub>42<\/jats:sub> (median = 846.2 pg\/mL; range = 238.8\u20133,707.0) than HCs at baseline (CSF t\u2010tau median = 173.5 pg\/mL; range = 82.0\u2013580.8; p\u2010tau median = 15.4 pg\/mL; range = 8.1\u201373.6; and A\u03b2<jats:sub>42<\/jats:sub> median = 926.5 pg\/mL; range = 239.1\u20133,297.0; <jats:italic>p<\/jats:italic> &lt;\u20090.05\u20130.001) and a moderate\u2010to\u2010strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50\u20130.97; <jats:italic>p<\/jats:italic> &lt;\u20090.001). Of the patients with PD, 31.5% had pathologically low levels of CSF A\u03b2<jats:sub>42<\/jats:sub> at baseline and these patients with PD had lower p\u2010tau levels (median = 10.8 pg\/mL; range = 8.0\u201332.8) compared with 27.7% of HCs with pathologically low CSF A\u03b2<jats:sub>42<\/jats:sub> (CSF p\u2010tau median = 12.8 pg\/mL; range 8.2\u201373.6; <jats:italic>p<\/jats:italic> &lt;\u20090.03)<jats:sub>.<\/jats:sub> In longitudinal CSF analysis, we found patients with PD had greater decline in CSF A\u03b2<jats:sub>42<\/jats:sub> (mean difference = \u221241.83 pg\/mL; <jats:italic>p<\/jats:italic> =\u20090.03) and CSF p\u2010tau (mean difference = \u22120.38 pg\/mL; <jats:italic>p<\/jats:italic> =\u20090.03) at year 3 compared with HCs. Baseline CSF A\u03b2<jats:sub>42<\/jats:sub> values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3\u2010year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020;88:574\u2013587<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25811","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T09:45:18Z","timestamp":1592300718000},"page":"574-587","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease"],"prefix":"10.1002","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-5098","authenticated-orcid":false,"given":"David J.","family":"Irwin","sequence":"first","affiliation":[{"name":"Department of Neurology School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janel","family":"Fedler","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Coffey","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Caspell\u2010Garcia","sequence":"additional","affiliation":[{"name":"Department of Biostatistics College of Public Health, University of Iowa  Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Clinical Pharmacology Inha University  Incheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Simuni","sequence":"additional","affiliation":[{"name":"Feinberg School of Medicine Northwestern University  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Foroud","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur W.","family":"Toga","sequence":"additional","affiliation":[{"name":"Laboratory of Neuro Imaging University of Southern California  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kieburtz","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center  Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana M.","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Reimer","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Hutten","sequence":"additional","affiliation":[{"name":"The Michael J. Fox Foundation  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-7168","authenticated-orcid":false,"given":"Daniel","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Department of Psychiatry Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Michael J. Crescenz VA Medical Center, Parkinson's Disease Research, Education, and Clinical Center  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center, G\u00f6ttingen Paracelsus\u2010Elena\u2010Klinik  Kassel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Galasko","sequence":"additional","affiliation":[{"name":"Department of Neurology University of San Diego  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Marek","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Q.","family":"Trojanowski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Center for Neurodegenerative Disease Research School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Parkinson's Progression Marker Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23659"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30291-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f39a78"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23287"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.199950"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22594"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005166"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1552-2"},{"key":"e_1_2_8_10_1","first-page":"1277","article-title":"Association of cerebrospinal fluid A\u03b21\u201042, t\u2010tau, p\u2010tau181 and \u03b1\u2010synuclein levels with clinical features of early drug na\u00efve Parkinson's disease patients","volume":"70","author":"Kang JH","year":"2013","journal-title":"JAMA Neurol"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1121-x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-318956"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004609"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.10.008"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26578"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0808-0"},{"key":"e_1_2_8_17_1","first-page":"698","article-title":"Derivation of cutoffs for the Elecsys((R)) amyloid beta (1\u201042) assay in Alzheimer's disease","volume":"10","author":"Shaw LM","year":"2018","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2016-1061"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.010"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.09.009"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.09.005"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175674"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26170"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0024338"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190069"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2019.05.006"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-301413"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp234"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25392"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000165987.89198.65"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2016.07.008"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21507"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24893"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002923"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.600"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1151-4"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.200900048"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160698"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.1654"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.015"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.644"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30328-3"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001098"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0647-x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2014.12.027"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000425"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-303808"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.12.007"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.01.018"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0157-7"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70291-0"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.25811","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25811","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.25811","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.25811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T19:17:36Z","timestamp":1693941456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.25811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,2]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1002\/ana.25811"],"URL":"https:\/\/doi.org\/10.1002\/ana.25811","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,2]]},"assertion":[{"value":"2019-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}