{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:51:03Z","timestamp":1760244663680,"version":"build-2065373602"},"reference-count":11,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2021R1A2C1093218","VHSMC20037"],"award-info":[{"award-number":["2021R1A2C1093218","VHSMC20037"]}]},{"name":"VHS Medical Center research grant, South Korea","award":["2021R1A2C1093218","VHSMC20037"],"award-info":[{"award-number":["2021R1A2C1093218","VHSMC20037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are associated with autosomal-dominant early-onset Alzheimer\u2019s disease (AD). Most mutations have been identified in the PSEN1 gene. We discovered a PSEN1 mutation (Tyr389His) in a Korean patient with early-onset AD who presented memory decline at 41 years of age followed by language, memory, and visuospatial dysfunctions. As this is the third such patient identified in Korea, this mutation may be involved in AD pathogenesis, suggesting that routine screening is necessary in this population. Altered intra-molecular interactions with the mutated amino acid may result in the destabilization of \u03b3-secretase. In the future, a panel incorporating genes with relatively high-frequency rare variants, along with the APOE4 gene, may predict the onset of AD and facilitate customized treatment.<\/jats:p>","DOI":"10.3390\/ijms232416192","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:25:46Z","timestamp":1671427546000},"page":"16192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of the Third Case of PSEN1 Tyr389His Variant in Early-Onset Alzheimer\u2019s Disease in Korea"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5402-337X","authenticated-orcid":false,"given":"Kyu Hwan","family":"Shim","sequence":"first","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam-si 13120, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangjoon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-6183","authenticated-orcid":false,"given":"Seong Soo A.","family":"An","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam-si 13120, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-6073","authenticated-orcid":false,"given":"Min Ju","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1093\/hmg\/10.16.1665","article-title":"Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect Abeta secretion and APP C-terminal fragment stability","volume":"10","author":"Esselens","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E476","DOI":"10.1073\/pnas.1618657114","article-title":"Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase","volume":"114","author":"Sun","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1038\/emboj.2012.79","article-title":"The mechanism of \u03b3-Secretase dysfunction in familial Alzheimer disease","volume":"31","author":"Bammens","year":"2012","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Giau, V.V., Bagyinszky, E., Youn, Y.C., An, S.S.A., and Kim, S. (2019). APP, PSEN1, and PSEN2 Mutations in Asian Patients with Early-Onset Alzheimer Disease. Int. J. Mol. 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Aging Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s12311-020-01173-z","article-title":"Ataxia Associated with CADASIL: A Pathology-Confirmed Case Report and Literature Review","volume":"19","author":"Park","year":"2020","journal-title":"Cerebellum"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1002\/mds.28171","article-title":"Parkinson\u2019s Disease, NOTCH3 Genetic Variants, and White Matter Hyperintensities","volume":"35","author":"Ramirez","year":"2020","journal-title":"Mov. Disord."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16192\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:44:00Z","timestamp":1760147040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/16192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,19]]},"references-count":11,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232416192"],"URL":"https:\/\/doi.org\/10.3390\/ijms232416192","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,12,19]]}}}