{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:13:27Z","timestamp":1777396407397,"version":"3.51.4"},"reference-count":57,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T00:00:00Z","timestamp":1536019200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2018,10,16]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>To date, the therapeutic paradigm for Alzheimer\u2019s disease (AD) has focused on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25\u200amg once daily), naproxen (220\u200amg twice-daily) or placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>474 participants with mild-to-moderate AD were screened with 351 enrolled into the trial. Using support vector machine (SVM) analyses, 89% of the subjects randomized to either NSAID treatment arms were correctly classified using a general NSAID companion diagnostic. Drug-specific companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and 97% accuracy in the naproxen arm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Inflammatory-based companion diagnostics have significant potential to identify select patients with AD who have a high likelihood of responding to NSAID therapy. This work provides empirical support for a precision medicine model approach to treating AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-180619","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T14:52:09Z","timestamp":1536072729000},"page":"97-104","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"66","author":[{"given":"Sid E.","family":"O\u2019Bryant","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Neuroscience; Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vermont Genetics Network, University of Vermont, VT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Neuroscience; Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Neuroscience; Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Edwards","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Grammas","sequence":"additional","affiliation":[{"name":"George &amp; Anne Ryan Institute for Neuroscience, University of Rhode Island, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University, Baltimore, MD, USA"},{"name":"Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantine G.","family":"Lyketsos","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Rissman","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA"},{"name":"VA San Diego Healthcare System, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,9,4]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1204629"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2017.1287866"},{"key":"e_1_3_2_5_2","first-page":"243","article-title":"Precision Medicine: The Golden Gate for detection, treatment and prevention of Alzheimer\u2019s disease","volume":"3","author":"Hampel H OBS","year":"2016","unstructured":"HampelH OBS, CastrilloJI, RitchieC, RojkovaK, BendaN, NisticoR, FrankRA, DuboisB, Escott-PriceV, ListaS (2016) Precision Medicine: The Golden Gate for detection, treatment and prevention of Alzheimer\u2019s disease. J Prev Alzheimers Dis 3, 243\u2013259.","journal-title":"J Prev Alzheimers Dis"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2015.05.003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)01986-4"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103153441101"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2015.1002470"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.09.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0723-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-014-1293-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3705"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-017-0216-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205014666171004113537"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19818"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170093"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/1179573517722512"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)01359-5"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90035-3"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10265"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010178"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.11.2066"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-316201"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7407.128"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.215"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028092"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000330750"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141041"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.21.2819"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02743.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2005.07.004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205054367883"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/0891988709351832"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300690"},{"key":"e_1_3_2_36_2","first-page":"200","article-title":"Neither rofecoxib nor naproxen slows cognitive decline in people with mild-to-moderate Alzheimer\u2019s disease","volume":"7","author":"Aisen PS","year":"2003","unstructured":"AisenPS, SchaferKA, GrundmanM, KnopmanD, TabetN (2003) Neither rofecoxib nor naproxen slows cognitive decline in people with mild-to-moderate Alzheimer\u2019s disease. Evid Based Med 7, 200\u2013201.","journal-title":"Evid Based Med"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000260269.93245.d2"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.5.668"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.8.1165"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1159\/000071001"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2016.06.004"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-122074"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-141506"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2016.1200972"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300690"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.12.014"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(98)00013-8"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199611250-00057"},{"key":"e_1_3_2_50_2","first-page":"201","article-title":"Indomethacin reverses the microglial response to amyloid beta","volume":"19","author":"Netland EE NJ","year":"1998","unstructured":"Netland EENJ, MajochaRE, TateBA (1998) Indomethacin reverses the microglial response to amyloid beta. Protein 19, 201\u2013204.","journal-title":"Protein"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.4.986"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1609"},{"key":"e_1_3_2_53_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1006\/exnr.1997.6429","volume":"144","author":"Tocco G","year":"1997","unstructured":"ToccoG, Freire-MoarJ, SchreiberSS, SakhiSH, AisenPS, PasinettiGM (1997) Maturational regulation and regional induction of cyclooxygenase-2 in rat brain: Implications for Alzheimer\u2019s disease. Exp Neurol 144, 339\u2013349","journal-title":"Exp Neurol"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00218-8"},{"key":"e_1_3_2_55_2","unstructured":"Food & Drug Administration (2016) Principles for codevelopment of an in vitro diagnostic device with a therapeutic product. Rockville MD USA. https:\/\/www.federalregister.gov\/documents\/2016\/07\/15\/2016-16735\/principles-for-codevelopment-of-an-in-vitro-companion-diagnostic-device-with-a-therapeutic-product."},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311107"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1586\/14737159.2015.997713"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1006448"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-180619","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-180619","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-180619","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:11Z","timestamp":1777370891000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-180619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,4]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,10,16]]}},"alternative-id":["10.3233\/JAD-180619"],"URL":"https:\/\/doi.org\/10.3233\/jad-180619","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,4]]}}}