{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:51:50Z","timestamp":1790851910553,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"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. Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disease characterized by gradual cognitive decline. Early-onset Alzheimer\u2019s disease (EOAD) is defined as AD occurring before age 65. The main pathogenic gene variants associated with EOAD include <jats:italic>PSEN1<\/jats:italic>, <jats:italic>PSEN2<\/jats:italic>, and <jats:italic>APP. IDE<\/jats:italic> gene has been identified as a risk factor in the pathogenesis of AD. In this study, we report a 33-year-old male with mutations in the <jats:italic>PSEN2<\/jats:italic> gene (c.640G &amp;gt; T, p.V214L) and <jats:italic>IDE<\/jats:italic> gene (c.782G &amp;gt; A, p.R261Q). <jats:italic>PSEN2<\/jats:italic> V214L has been reported in five previous cases, and no reported cases have carried <jats:italic>IDE<\/jats:italic> R261Q. He had progressive memory decline, his sister carried the same gene mutations but had no clinical manifestations. Neuroimaging revealed mild cortical atrophy. The concentration of A\u03b242 in cerebrospinal fluid (CSF) was obviously decreased. In silico predictive models suggested that these mutations are damaging. Our findings indicate that mutations in the <jats:italic>PSEN2<\/jats:italic> and <jats:italic>IDE<\/jats:italic> genes may disrupt the normal functioning of their respective proteins, contributing to the pathogenesis of AD.<\/jats:p>","DOI":"10.3389\/fnins.2024.1423892","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:05:05Z","timestamp":1730293505000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Case report: Double mutations in a patient with early-onset Alzheimer\u2019s disease in China, PSEN2 and IDE variants"],"prefix":"10.3389","volume":"18","author":[{"given":"Zhongzheng","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caibin","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianli","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0102995","article-title":"Widespread disruption of functional brain organization in early-onset Alzheimer\u2019s disease.","volume":"9","author":"Adriaanse","year":"2014","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1212\/wnl.36.11.1497","article-title":"Origin of the distinction between Alzheimer\u2019s disease and senile dementia: How history can clarify nosology.","volume":"36","author":"Amaducci","year":"1986","journal-title":"Neurology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.2147\/CIA.S116724","article-title":"A genetic screen of the mutations in the Korean patients with early-onset Alzheimer\u2019s disease.","volume":"11","author":"An","year":"2016","journal-title":"Clin. 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