{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:26:55Z","timestamp":1790807215566,"version":"4.1.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"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><jats:title>Objective<\/jats:title><jats:p>Aquaporin-4 (AQP4) facilitates a sleep-enhanced interstitial brain waste clearance system. This study was conducted to determine the clinical implication of <jats:italic>AQP4<\/jats:italic> polymorphisms in Parkinson\u2019s disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three-hundred and eighty-two patients with PD and 180 healthy controls with a mean follow-up time of 66.1 months from the Parkinson\u2019s Progression Marker Initiative study were analyzed. We examined whether <jats:italic>AQP4<\/jats:italic> SNPs were associated with an altered rate of motor or cognitive decline using linear mixed model and Cox regression. We then investigated whether <jats:italic>AQP4<\/jats:italic> SNPs were associated with A\u03b2 burden as measured by <jats:sup>18<\/jats:sup>F Florbetapir standard uptake values. Furthermore, we examined if <jats:italic>AQP4<\/jats:italic> SNPs moderated the association between REM sleep behavior disorder (RBD) and CSF biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients with PD, <jats:italic>AQP4<\/jats:italic> rs162009 (AA\/AG vs. GG) was associated with slower dementia conversion, better performance in letter-number sequencing and symbol digit modalities, lower A\u03b2 deposition in the putamen, anterior cingulum, and frontotemporal areas. In the subgroup of high RBD screening questionnaire score, rs162009 AA\/AG had a higher CSF A\u03b242 level. rs162009 AA\/AG also had better performance in semantic fluency in healthy controls. Besides, rs68006382 (GG\/GA vs. AA) was associated with faster progression to mild cognitive impairment, worse performance in letter-number sequencing, semantic fluency, and symbol digit modalities in patients with PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Genetic variations of <jats:italic>AQP4<\/jats:italic> and subsequent alterations of glymphatic efficacy might contribute to an altered rate of cognitive decline in PD. <jats:italic>AQP4<\/jats:italic> rs162009 is likely a novel genetic prognostic marker of glymphatic function and cognitive decline in PD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2021.740491","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T14:35:58Z","timestamp":1646836558000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Aquaporin-4 Polymorphisms Are Associated With Cognitive Performance in Parkinson\u2019s Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Yi","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobing","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhen","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baorong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1212\/WNL.0b013e318253d54b","article-title":"Cognitive performance of GBA mutation carriers with early-onset PD","volume":"78","author":"Alcalay","year":"2012","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1212\/WNL.0000000000000425","article-title":"CSF A\u03b242 predicts early-onset dementia in Parkinson disease","volume":"82","author":"Alves","year":"2014","journal-title":"Neurology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1179\/1743132815Y.0000000047","article-title":"Aquaporin-4 gene variant independently associated with oedema after intracerebral haemorrhage","volume":"37","author":"Appelboom","year":"2015","journal-title":"Neurol. 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