{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:39:38Z","timestamp":1787315978240,"version":"build-2736575974"},"reference-count":54,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"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":[[2020,10,13]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Rare variants in\n                      <jats:italic toggle=\"yes\">PLCG2<\/jats:italic>\n                      (p.P522R),\n                      <jats:italic toggle=\"yes\">ABI3<\/jats:italic>\n                      (p.S209F), and\n                      <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                      (p.R47H, p.R62H) have been associated with late onset Alzheimer\u2019s disease (LOAD) risk in Caucasians. After the initial report, several studies have found positive results in cohorts of different ethnic background and with different phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      In this study, we aim to evaluate the association of rare coding variants in\n                      <jats:italic toggle=\"yes\">PLCG2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">ABI3<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                      with LOAD risk and their effect at different time points of the disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We used a European American cohort to assess the association of the variants prior onset (using CSF A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      , tau, and pTau levels, and amyloid imaging as endophenotypes) and after onset (measured as rate of memory decline).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We confirm the association with LOAD risk of\n                      <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                      p.R47H, p.R62H and\n                      <jats:italic toggle=\"yes\">ABI3<\/jats:italic>\n                      p.S209F variants, and the protective effect of\n                      <jats:italic toggle=\"yes\">PLCG2<\/jats:italic>\n                      p.P522R. In addition,\n                      <jats:italic toggle=\"yes\">ABI3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                      gene-sets showed significant association with LOAD risk.\n                      <jats:italic toggle=\"yes\">TREM2<\/jats:italic>\n                      p.R47H and\n                      <jats:italic toggle=\"yes\">PLCG2<\/jats:italic>\n                      p.P522R variants were also statistically associated with increase of amyloid imaging and AD progression, respectively. We did not observe any association of\n                      <jats:italic toggle=\"yes\">ABI3<\/jats:italic>\n                      p.S209F with any of the other AD endophenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The results of this study highlight the importance of including biomarkers and alternative phenotypes to better understand the role of novel candidate genes with the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-200019","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T12:15:06Z","timestamp":1599221706000},"page":"1469-1482","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["Examination of the Effect of Rare Variants in\n                    <i>TREM2<\/i>\n                    ,\n                    <i>ABI3<\/i>\n                    , and\n                    <i>PLCG2<\/i>\n                    in LOAD Through Multiple Phenotypes"],"prefix":"10.1177","volume":"77","author":[{"given":"Claudia","family":"Olive","sequence":"first","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ibanez","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana H. Geraldo","family":"Farias","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Budde","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne B.","family":"Norton","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen","family":"Gentsch","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Morris","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeran","family":"Li","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umber","family":"Dube","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Del-Aguila","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristy","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Bradley","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno A.","family":"Benitez","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Harari","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fagan","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau","family":"Ances","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Cruchaga","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Victoria","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine","place":["USA"]},{"name":"Washington University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2741\/E605"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202753"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.041"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.03.025"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0158-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0358-2"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170834"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0311-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.02.024"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2015.07.008"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00209"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12825"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211851"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211103"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0016-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3916"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-019-0394-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2019.03.005"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02026-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0289-x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-091711"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1685-y"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.02.026"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/0891988705281881"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031039"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2412-a"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.122"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.08.013"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20730"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181bc010c"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.11.032"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21843"},{"key":"e_1_3_3_36_2","unstructured":"R Core Team (2018) R: A language and environment for statistical computing. R Found Stat Comput Vienna Austria."},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxs014"},{"key":"e_1_3_3_40_2","first-page":"1589","article-title":"Whole exome sequencing study identifies novel rare and common Alzheimer\u2019s-Associated variants involved in immune response and transcriptional regulation","volume":"25","author":"Bis JC","year":"2018","unstructured":"BisJC, JianX, KunkleBW, ChenY, Hamilton-NelsonKL, BushWS, SalernoWJ, LancourD, MaY, RentonAE, MarcoraE, FarrellJJ, ZhaoY, QuL, AhmadS, AminN, AmouyelP, BeechamGW, BelowJE, CampionD, CharbonnierC, ChungJ, CranePK, CruchagaC, CupplesLA, DartiguesJF, DebetteS, DeleuzeJF, FultonL, GabrielSB, GeninE, GibbsRA, GoateA, Grenier-BoleyB, GuptaN, HainesJL, HavulinnaAS, HelisalmiS, HiltunenM, HowriganDP, IkramMA, KaprioJ, KonradJ, KuzmaA, LanderES, LathropM, Lehtim\u00e4kiT, LinH, MattilaK, MayeuxR, MuznyDM, NasserW, NealeB, NhoK, NicolasG, PatelD, Pericak-VanceMA, PerolaM, PsatyBM, QuenezO, RajabliF, RedonR, ReitzC, RemesAM, SalomaaV, SarnowskiC, SchmidtH, SchmidtM, SchmidtR, SoininenH, ThorntonTA, TostoG, TzourioC, van der LeeSJ, van DuijnCM, VardarajanB, WangW, WijsmanE, WilsonRK, WittenD, WorleyKC, ZhangX, BellenguezC, LambertJC, KurkiMI, PalotieA, DalyM, BoerwinkleE, LunettaKL, DestefanoAL, DupuisJ, MartinER, SchellenbergGD, SeshadriS, NajAC, FornageM, FarrerLA (2018) Whole exome sequencing study identifies novel rare and common Alzheimer\u2019s-Associated variants involved in immune response and transcriptional regulation. Mol Psychiatry 25, 1589\u20131875.","journal-title":"Mol Psychiatry"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu277"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.07.004"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.02.023"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.12.009"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.08.001"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1159\/000452256"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000275"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-122311"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.12.018"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.08.011"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.04.012"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.05.1751"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000855"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2018.1486823"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0469-0"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200019","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-200019","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-200019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:48Z","timestamp":1777370928000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-200019"}},"subtitle":[],"editor":[{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,9,4]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,10,13]]}},"alternative-id":["10.3233\/JAD-200019"],"URL":"https:\/\/doi.org\/10.3233\/jad-200019","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,4]]}}}