{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:04:33Z","timestamp":1790665473859,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018231","name":"Aligning Science Across Parkinson's","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018231","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2488"],"award-info":[{"award-number":["FOR2488"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Heisenberg Grant (TR1714\/8\u20101)"],"award-info":[{"award-number":["Heisenberg Grant (TR1714\/8\u20101)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. 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Lundbeck A\/S","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018556","name":"Voyager Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018556","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reliable biomarkers for Parkinson's disease (PD) pathology detection are essential for research. \u03b1\u2010Synuclein (aSyn) seed amplification assay (SAA) is a validated biomarker for misfolded aSyn.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      The aim was to assess the association between aSyn SAA and\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010related PD (\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD) and its link to mitochondrial genetic burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included N\u2009=\u200976 LRRK2 p.Gly2019Ser variant carriers (N\u2009=\u200922 affected, N\u2009=\u200954 unaffected), N\u2009=\u2009714 patients with idiopathic PD (iPD), and N\u2009=\u2009411 controls from Norway. We analyzed cerebrospinal fluid (CSF)\u2013based aSyn SAA in N\u2009=\u200910 PD patients and N\u2009=\u200930 unaffected LRRK2 p.Gly2019Ser carriers, alongside N\u2009=\u20096 controls and N\u2009=\u200956 iPD patients. A mitochondrial polygenic score (MGS) was derived from genotyping data, using Parkinson's Progression Markers Initiative (PPMI) as an additional cohort (iPD: N\u2009=\u2009355,\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD: N\u2009=\u2009118). In patients with PD, we explored the association between mitochondrial genetic burden and aSyn SAA outcome as well as SAA kinetic measurements.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seeding was observed in 80% of patients with\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD and in 1 unaffected variant carrier (AUC\u2009=\u20090.97, confidence interval [CI] 0.92\u20131.00). In an exploratory meta\u2010analysis across 2 PD cohorts, higher MGS was associated with increased aSyn seeding (pooled \u03b2\u2009=\u20090.43, odds ratio [OR]\u2009=\u20091.54,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.014). In the Norwegian cohort, assessing aSyn SAA kinetic measurements, higher MGS was associated with a higher maximum slope (\u03b2\u2009=\u20091.22, standard error [SE]\u2009=\u20090.50,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.020). In PPMI, higher MGS was associated with shorter time to threshold (\u03b2\u2009=\u2009\u22120.34, SE\u2009=\u20090.13,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.007) and time to maximum slope (\u03b2\u2009=\u2009\u22120.35, SE\u2009=\u20090.13,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.007).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CSF\u2010based aSyn SAA can discriminate between\n                      <jats:italic>LRRK2<\/jats:italic>\n                      \u2010PD and unaffected carriers. Our findings suggest an association between mitochondrial genetic burden and aSyn seeding. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70553","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:23:08Z","timestamp":1790662988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1\u2010Synuclein Seeding Discriminates Between\n                    <scp>LRRK2 G2019S<\/scp>\n                    Variant Carriers with and Without Parkinson's Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-0498","authenticated-orcid":false,"given":"Theresa","family":"L\u00fcth","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-9330","authenticated-orcid":false,"given":"Carolin","family":"Gabbert","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6313-7395","authenticated-orcid":false,"given":"Teresa","family":"Kleinz","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein  L\u00fcbeck Germany"},{"name":"Department of Neurology University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Much","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck and University Hospital Schleswig\u2010Holstein  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9265-5738","authenticated-orcid":false,"given":"Bj\u00f6rn\u2010Hergen","family":"Laabs","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Department of Medical Statistics University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1635-4247","authenticated-orcid":false,"given":"Sebastian","family":"Sendel","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics Kiel University and University Hospital Schleswig\u2010Holstein  Kiel Germany"},{"name":"Institute of Clinical Research and Digitalization, Medical Faculty Health and Medical University Erfurt  Erfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-6465","authenticated-orcid":false,"given":"Inke R.","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0340-9154","authenticated-orcid":false,"given":"Amke","family":"Caliebe","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics Kiel University and University Hospital Schleswig\u2010Holstein  Kiel Germany"},{"name":"Institute of Clinical Research and Digitalization, Medical Faculty Health and Medical University Erfurt  Erfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-5321","authenticated-orcid":false,"given":"Matthew","family":"Farrer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8797-2042","authenticated-orcid":false,"given":"Brian","family":"Fiske","sequence":"additional","affiliation":[{"name":"The Michael J. 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