{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:54:04Z","timestamp":1777888444607,"version":"3.51.4"},"reference-count":21,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,2,17]],"date-time":"2018-02-17T00:00:00Z","timestamp":1518825600000},"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 Parkinson\u2019s Disease"],"published-print":{"date-parts":[[2018,2,17]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Mutations in the leucine rich repeat kinase 2 ( LRRK2) gene are among the most common genetic causes of Lewy body Parkinson\u2019s disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To genetically and pathologically characterize a case with a LRRK2, p.Ile1371Val rare variant and pathologically proven MSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>From the brain donation program at the Parkinson\u2019s Institute and Clinical Center, we selected 26 brains with family history and a with clinicopathological diagnosis of PD ( n\u200a=\u200a20), MSA ( n\u200a=\u200a4), or PSP ( n\u200a=\u200a2). We performed neuropathological evaluation, including alpha-synuclein and tau immunohistochemistry and sequenced 188 genes that have been reported as causative for or associated with neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We identified a known LRRK2, p.Ile1371Val genetic variant in a case with clinically diagnosed and pathologically proven MSA. Neuropathology revealed that the olivopontocerebellar system was more affected than the striatonigral system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our data suggest that genetic variants in the LRRK2 gene can present clinically and neuropathologically as MSA. One other LRRK2 genetic variant ( LRRK2, p.Ile2020Thr) has been reported with a neuropathological diagnosis of MSA. Interestingly, the LRRK2 variant ( LRRK2, p.Ile1371Val) identified here has been reported previously in a postmortem case with Lewy body PD. Future studies are critical to discover the mechanisms leading to different neurodegenerative trajectories both in neuronal and glial cell populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jpd-171237","type":"journal-article","created":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T11:45:27Z","timestamp":1519127127000},"page":"93-100","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["LRRK2 p.Ile1371Val Mutation in a Case with Neuropathologically Confirmed Multi-System Atrophy"],"prefix":"10.1177","volume":"8","author":[{"given":"Kelsey","family":"Lee","sequence":"first","affiliation":[{"name":"Parkinson\u2019s Institute and Clinical Center, Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khanh-Dung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Sun","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faria","family":"Zafar","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Institute and Clinical Center, Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jimmy","family":"Saetern","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Institute and Clinical Center, Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Flierl","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Institute and Clinical Center, Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Tetrud","sequence":"additional","affiliation":[{"name":"Stanford Neuroscience Health Center, Stanford School of Medicine, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. William","family":"Langston","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Institute and Clinical Center, Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitt","family":"Sch\u00fcle","sequence":"additional","affiliation":[{"name":"Parkinson\u2019s Institute and Clinical Center, Sunnyvale, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,2,17]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.005"},{"key":"ref002","volume-title":"GeneReviews(R)","author":"Trinh J","year":"1993"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70175-2"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3454"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000125015.06989.DB"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000240220.33950.0c"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-0991-7"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.2704"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21281"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000167552.79769.b3"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201539"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.062612"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2015.04.002"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23283"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.79"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2008.07.010"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100483"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1017\/S1740925X04000043"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1007\/PL00007400"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051177"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1789.2001.00390.x"}],"container-title":["Journal of Parkinson\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-171237","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JPD-171237","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JPD-171237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:46:01Z","timestamp":1777610761000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JPD-171237"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,17]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,2,17]]}},"alternative-id":["10.3233\/JPD-171237"],"URL":"https:\/\/doi.org\/10.3233\/jpd-171237","relation":{},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,17]]}}}