{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:06:51Z","timestamp":1753891611476,"version":"3.41.2"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p><jats:bold>Introduction<\/jats:bold>: Two common variants of sortilin-related receptor 1 gene (<jats:italic>SORL1<\/jats:italic>), rs2298813 and rs1784933, have been associated with late-onset Alzheimer\u2019s disease (AD) in the Han Chinese population in Taiwan. However, neuroimaging correlates of these two <jats:italic>SORL1<\/jats:italic> variants remain unknown. We aimed to determine whether the two <jats:italic>SORL1<\/jats:italic> polymorphisms were associated with any volumetric differences in brain regions in late-onset AD patients.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: We recruited 200 patients with late-onset AD from Taipei Veterans General Hospital. All patients received a structural magnetic resonance (MR) imaging brain scan and completed a battery of neurocognitive tests at enrollment. We followed up to assess changes in Mini-Mental State Examination (MMSE) scores in 155 patients (77.5%) at an interval of 2 years. Volumetric measures and cortical thickness of various brain regions were performed using FreeSurfer. Regression analysis controlled for apolipoprotein E status. Multiple comparisons were corrected for using the false discovery rate.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: The homozygous major allele of rs2298813 was associated with larger volumes in the right putamen (<jats:italic>p<\/jats:italic> = 0.0442) and right pallidum (<jats:italic>p<\/jats:italic> = 0.0346). There was no link between the rs1784933 genotypes with any regional volume or thickness of the brain. In the rs2298813 homozygous major allele carriers, the right putaminal volume was associated with verbal fluency (<jats:italic>p<\/jats:italic> = 0.008), and both the right putaminal and pallidal volumes were predictive of clinical progression at follow-up (<jats:italic>p<\/jats:italic> = 0.020). In the minor allele carriers, neither of the nuclei was related to cognitive test performance or clinical progression.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>: The major and minor alleles of rs2298813 had differential effects on the right lentiform nucleus volume and distinctively modulated the association between the regional volume and cognitive function in patients with AD.<\/jats:p>","DOI":"10.3389\/fnagi.2022.885090","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T10:56:05Z","timestamp":1659696965000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Endophenotypic effects of the SORL1 variant rs2298813 on regional brain volume in patients with late-onset Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Chun-Yu","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Shuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Ju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Chu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shan","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert C.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Ling","family":"Fuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/0166-2236(89)90074-x","article-title":"The functional anatomy of basal ganglia disorders","volume":"12","author":"Albin","year":"1989","journal-title":"Trends Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1159\/000332017","article-title":"Impact of SORL1 single nucleotide polymorphisms on Alzheimer\u2019s disease cerebrospinal fluid markers","volume":"32","author":"Alexopoulos","year":"2011","journal-title":"Dement. 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