{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:18:21Z","timestamp":1787509101711,"version":"build-2736575974"},"reference-count":62,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M741857"],"award-info":[{"award-number":["2023M741857"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023TQ0165"],"award-info":[{"award-number":["2023TQ0165"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471459"],"award-info":[{"award-number":["82471459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018936","name":"Qingdao Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["QDBSH20230202039"],"award-info":[{"award-number":["QDBSH20230202039"]}],"id":[{"id":"10.13039\/100018936","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020196","name":"Shandong Provincial Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["SDBX2023050"],"award-info":[{"award-number":["SDBX2023050"]}],"id":[{"id":"10.13039\/501100020196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020196","name":"Shandong Provincial Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["SDCX\u2010ZG\u2010202400038"],"award-info":[{"award-number":["SDCX\u2010ZG\u2010202400038"]}],"id":[{"id":"10.13039\/501100020196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Leukocyte immunoglobulin\u2010like receptor B4 (LILRB4) has been shown to be associated with susceptibility to neurodegenerative diseases. This study was aimed at investigating the relationships between\n LILRB4<\/jats:italic>\n and the risk of developing PD, as well as its clinical characteristics and pathology.\n <\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n We analyzed 197 healthy controls and 606 PD patients from the Parkinson's Progression Marker Initiative (PPMI) study. The associations of\n LILRB4<\/jats:italic>\n loci with image data, CSF biomarkers, and clinical scales at baseline were assessed using multiple linear models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Dopamine transporter (DAT)\u2010SPECT results showed that the striatal binding ratios (SBR) in the right caudate (\n \u03b2<\/jats:italic>\n \u2009=\u20090.160, 95% CI\u2009=\u20090.076\u20130.244,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.002), right putamen (\n \u03b2<\/jats:italic>\n \u2009=\u20090.135, 95% CI\u2009=\u20090.057\u20130.214,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.009), anterior right putamen (\n \u03b2<\/jats:italic>\n \u2009=\u20090.156, 95% CI\u2009=\u20090.073\u20130.240,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.003) and left caudate (\n \u03b2<\/jats:italic>\n \u2009=\u20090.121, 95% CI\u2009=\u20090.038\u20130.2050,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.048) were positively associated with\n LILRB4<\/jats:italic>\n . Meanwhile,\n LILRB4<\/jats:italic>\n was associated with reductions in semantic fluency (\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22122.135, 95% CI\u2009=\u2009\u22123.225 to 1.046,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.001) and impairments in nigrostriatal white matter (WM) microstructure as assessed by diffusion tensor imaging (DTI) (right rostral of substantia nigra (SN),\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22120.026, 95% CI\u2009=\u2009\u22120.030 to 0.013,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.002; right middle SN,\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22120.021, 95% CI\u2009=\u2009\u22120.033 to 0.009,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.012). These associations were more prominent in females (DAT in right caudate,\n \u03b2<\/jats:italic>\n \u2009=\u20090.246, 95% CI\u2009=\u20090.099\u20130.392,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.013; DTI in right middle of SN,\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22120.025 95% CI\u2009=\u2009\u22120.040 to 0.010,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.021), but less pronounced in males (DAT in right caudate,\n p<\/jats:italic>\n \u2009=\u20090.036,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.396; DTI in right rostral of SN,\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22120.025 95% CI\u2009=\u2009\u22120.041 to 0.008,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.021). Interestingly, in females, we also observed associations between\n LILRB4<\/jats:italic>\n and higher CSF \u03b1\u2010synuclein levels (\n \u03b2<\/jats:italic>\n \u2009=\u20090.177, 95% CI\u2009=\u20090.062\u20130.292,\n p<\/jats:italic>\n \u2009=\u20093.280E\u221203,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.036) and worse cognitive performance (Activity of Daily Living scale,\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22122.073, 95% CI\u2009=\u2009\u22123.446 to 0.699,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.025; Semantic Fluency test,\n \u03b2<\/jats:italic>\n \u2009=\u2009\u22122.508 95% CI\u2009=\u2009\u22124.255 to 0.761,\n P<\/jats:italic>\n c<\/jats:sub>\n \u2009=\u20090.032). Although our results suggested that dopamine and its metabolites, astrocyte markers, and inflammation\u2010related molecules were associated with\n LILRB4<\/jats:italic>\n , these associations disappeared after false discovery rate (FDR) correction (\n p<\/jats:italic>\n \u2009\u2264\u20090.05, but\n P<\/jats:italic>\n c<\/jats:sub>\n >\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our study supposes that LILRB4 may play a crucial role in modulating PD clinical characteristics by influencing nigrostriatal dopaminergic neuron function, Alzheimer's disease (AD)\u2010related pathology, WM microstructural alterations, and astrocyte activation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cns.70522","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T05:50:23Z","timestamp":1753336223000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Uncovering the Associations 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