{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:06:06Z","timestamp":1784786766945,"version":"3.55.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Transmembrane protein 106B (\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      ) variations not only act as genetic modifiers of the risk of developing frontotemporal lobar degeneration but also correlate with the heterogeneity of clinicopathological phenotypes in other neurodegenerative diseases. However, the roles of TMEM106B in Parkinson\u2019s disease (PD) are sparsely explored. This study aims to explore whether\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      variants influence the trajectories of clinical phenotypes in PD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We longitudinally followed 241 PD patients and genotyped their single nucleotide polymorphism (SNP) of rs3173615. Patients were categorized according to rs3173615 genotypes into GG (major allele homozygotes), GC (heterozygotes), and CC (minor allele homozygotes) groups. All patients completed clinical evaluations and neuropsychological tests at baseline and every follow-up. Linear mixed-effects models were adopted to evaluate the association between rs3173615 genotypes and longitudinal disease progression in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, both the GG and GC groups presented less severe excessive daytime sleepiness than the CC group, and no association between the remaining clinical characteristics and the genotypes of rs3173615 was observed among the three groups. Longitudinally, compared with the CC group, the GC group manifested a significantly faster exacerbation of depression, visuospatial function and quality of life (QoL), and the GG group showed the same tendency as the GC group, though without statistical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      rs3173615 is a genetic modifier for the trajectory of depression, visuospatial function and QoL in PD. Our findings suggest the potential involvement of TMEM106B in the pathogenesis of disease progression in PD, especially in the deterioration of depression, cognition and QoL.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1873947","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:39:01Z","timestamp":1784785141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of transmembrane protein 106B genetic variations on disease progression in Parkinson\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Wanbing","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoniu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bolin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Practice, Longgang District Central Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology and National Research Center for Aging and Medicine and National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1093\/hmg\/dds475","article-title":"The frontotemporal lobar degeneration risk factor, TMEM106B, regulates lysosomal morphology and function","volume":"22","author":"Brady","year":"2013","journal-title":"Hum. 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