{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:06:49Z","timestamp":1784678809583,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008539","name":"CurePSP","doi-asserted-by":"publisher","award":["681\u20102022\/06"],"award-info":[{"award-number":["681\u20102022\/06"]}],"id":[{"id":"10.13039\/100008539","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011707","name":"PSP Association","doi-asserted-by":"publisher","award":["PSPA2023\/PROJECTGRANT001"],"award-info":[{"award-number":["PSPA2023\/PROJECTGRANT001"]}],"id":[{"id":"10.13039\/100011707","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["UKRI1388"],"award-info":[{"award-number":["UKRI1388"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Common and rare genetic variants in leucine\u2010rich repeat kinase 2 (LRRK2) have been linked with sporadic and familial Parkinson's disease (PD). Recently, we discovered that common genetic variation near the LRRK2 locus determined survival in progressive supranuclear palsy (PSP). Our study aimed to explore biomarkers of LRRK2 and lysosomal dysfunction in PSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Immunoblotting was used to measure total LRRK2 and LRRK2\u2010dependent Rab10 phosphorylation at the threonine 73 residue (pRab10\n                      <jats:sup>Thr73<\/jats:sup>\n                      ) in neutrophil and monocyte samples from PSP and control participants. Urine samples were applied to a multiplexed assay to quantitate bis(monoacylglycerol)phosphate (BMP) species as markers of lysosomal dysfunction. Cerebrospinal fluid (CSF) samples from a wider cohort of PSP and control participants were applied to a stable isotope standards and capture by anti\u2010peptide antibodies assay to measure total LRRK2 and pRab10\n                      <jats:sup>Thr73<\/jats:sup>\n                      levels. LRRK2 genotypes (rs76904798 and rs2242367) and 1\u2010year change in Progressive Supranuclear Palsy Rating Scale (PSPRS) scores were obtained.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 61 PSP and 34 control participants were included. Total urine 22:6\u2010BMP levels were higher in PSP versus control samples (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04) and correlated with CSF total LRRK2 levels (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.49,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04). There were no group\u2010level differences in monocyte and CSF levels of total LRRK2 and pRab10\n                      <jats:sup>Thr73<\/jats:sup>\n                      . In PSP, carriers of the alternate allele (CT and TT genotypes) at the LRRK2 PD risk variant, rs76904798, had higher levels of CSF total LRRK2 versus CC genotype (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02). Baseline monocyte total LRRK2 levels predicted 1\u2010year change in the PSPRS score (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Biochemically defined lysosomal dysfunction is evident in PSP. Genetic and biochemical stratification may identify PSP patients that would benefit from LRRK2\u2010targeting therapies. \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.70295","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:14:51Z","timestamp":1776320091000},"page":"1740-1749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomarkers of Leucine\u2010Rich Repeat Kinase 2 (\n                    <scp>LRRK2)<\/scp>\n                    and Lysosomal Dysfunction in Progressive Supranuclear Palsy"],"prefix":"10.1002","volume":"41","author":[{"given":"Louise\u2010Kristine","family":"Nielsen","sequence":"first","affiliation":[{"name":"Medical Research Council Protein Phosphorylation and Ubiquitylation Unit University of Dundee  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9729-0077","authenticated-orcid":false,"given":"Joshua L.I.","family":"Frost","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Real","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riona","family":"Fumi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marte Theilmann","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor J.","family":"Stafford","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Ansorge","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies","family":"Quaegebeur","sequence":"additional","affiliation":[{"name":"Department of Histopathology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"},{"name":"Department of Imaging and Pathology University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieren S.J.","family":"Allinson","sequence":"additional","affiliation":[{"name":"Department of Histopathology Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas T.","family":"Warner","sequence":"additional","affiliation":[{"name":"Reta Lila Weston Institute UCL Queen Square Institute of Neurology  London UK"},{"name":"Queen Square Brain Bank for Neurological Disorders UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-8881","authenticated-orcid":false,"given":"Zane","family":"Jaunmuktane","sequence":"additional","affiliation":[{"name":"Reta Lila Weston Institute UCL Queen Square Institute of Neurology  London UK"},{"name":"Queen Square Brain Bank for Neurological Disorders UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjum","family":"Misbahuddin","sequence":"additional","affiliation":[{"name":"Department of Neurology Queen's Hospital  Romford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Nigel","family":"Leigh","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Brighton and Sussex Medical School University of Brighton and University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyd C.P.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Wessex Neurological Centre University Hospitals Southampton NHS Foundation Trust  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash P.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement Disorders Centre UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Church","sequence":"additional","affiliation":[{"name":"Department of Neurology Royal Gwent Hospital  Newport UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7797-0756","authenticated-orcid":false,"given":"Christopher","family":"Kobylecki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele T.M.","family":"Hu","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-8679","authenticated-orcid":false,"given":"James B.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, Cambridge University Hospitals NHS Trust and MRC Cognition and Brain Sciences Unit University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan A.","family":"Shomo","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle L.","family":"Graham","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar S.","family":"Mabrouk","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Unit, Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-3774","authenticated-orcid":false,"given":"Huw R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"},{"name":"Movement 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Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70295","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70295","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70295","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:59:34Z","timestamp":1784678374000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/mds.70295"],"URL":"https:\/\/doi.org\/10.1002\/mds.70295","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"assertion":[{"value":"2025-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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