{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:20:53Z","timestamp":1791202853194,"version":"4.2.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare","award":["RS-2024-00403047"],"award-info":[{"award-number":["RS-2024-00403047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Preclinical and epidemiologic data suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce the risk of Parkinson\u2019s disease and related disorders (PDRD), yet clinical trial findings have been mixed, raising the possibility of biologically meaningful heterogeneity. We tested whether interindividual differences in systemic GLP1R expression are associated with PDRD risk among adults with type 2 diabetes initiating GLP-1RAs. We conducted an electronic health record-based new-user cohort study in the National Institutes of Health All of Us Research Program, focusing on adults with type 2 diabetes aged 50 years or older who initiated a GLP-1RA between 2005 and 2023 and had no prior PDRD or Alzheimer\u2019s disease and related dementias (ADRD). Systemic GLP1R expression was genetically proxied by a 15-variant cis-expression quantitative trait locus (cis-eQTL) genetic risk score dichotomized at the cohort median. Follow-up ended at the earliest of incident PDRD, death or 1 October 2023. Hazard ratios (HR) were estimated using multivariable Cox proportional hazards models adjusting for baseline covariates, and incidence rates and rate differences per 1000 person-years were estimated using Poisson models. Prespecified sensitivity analyses excluded early outcome events and short drug exposure; an exploratory analysis evaluated incident ADRD.<\/jats:p>\n                  <jats:p>The cohort included 7039 initiators (3520 high versus 3519 low genetic score; mean age 61.7 \u00b1 8.4 years; 59.8% female; mean follow-up 3.8 \u00b1 3.1 years). Compared with the low-score group, the high-score group had a lower hazard of incident PDRD [HR 0.78; 95% confidence interval (CI) 0.62 to 0.98] and a lower incidence rate (rate difference \u22121.36 per 1000 person-years; 95% CI \u22122.51 to \u22120.20). Associations were consistent across sensitivity analyses. No association was observed for incident ADRD (HR 1.02; 95% CI 0.81 to 1.28).<\/jats:p>\n                  <jats:p>These findings link a mechanism-anchored genetic proxy for higher systemic GLP1R expression to a lower risk of incident PDRD among GLP-1RA-treated adults with type 2 diabetes. Systemic GLP1R-mediated pathways may be relevant to interindividual differences in observed PDRD risk, and genetic instruments for GLP1R expression may inform hypotheses for future PDRD trial design.<\/jats:p>","DOI":"10.1093\/brain\/awag130","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:46:05Z","timestamp":1775821565000},"page":"3431-3439","source":"Crossref","is-referenced-by-count":0,"title":["<i>GLP1R<\/i>\n                    expression and Parkinson\u2019s disease and related disorders in GLP-1 receptor agonist-treated type 2 diabetes"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5457-7348","authenticated-orcid":false,"given":"Kyung Ah","family":"Woo","sequence":"first","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Biomedical Research Institute, Seoul National University Hospital , Seoul 03080 ,","place":["Republic of Korea"]},{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5991-7822","authenticated-orcid":false,"given":"Yoonhyuk","family":"Jang","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Seoul National University Hospital , Seoul 03080 ,","place":["Republic of Korea"]},{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]},{"name":"Department of Immunology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-9663","authenticated-orcid":false,"given":"Han-Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine , Seoul 03080 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9378-960X","authenticated-orcid":false,"given":"Peter J","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"2026100419575182200_awag130-B1","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson 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