{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:09:53Z","timestamp":1778670593540,"version":"3.51.4"},"reference-count":32,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"The National key R&D Program of China","award":["2017YFC0909100"],"award-info":[{"award-number":["2017YFC0909100"]}]},{"name":"Science and Technology Development Project of Shandong Province","award":["2012G0021842"],"award-info":[{"award-number":["2012G0021842"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The majority of early-onset familial Alzheimer\u2019s disease is caused by mutations in the presenilin 1 (\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      ) gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate the pathogenic mechanism of the novel nucleotide mutations of the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      gene in early-onset familial Alzheimer's disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We describe a Chinese family with autosomal dominant early-onset Alzheimer\u2019s disease. Gene sequencing revealed that the 417th nucleotide in the exon 5 of the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      gene had changed from G to C. This resulted in methionine being substituted by isoleucine at codon 139. To support that the novel mutation was pathological, we transfected lentiviruses that overexpressed wild-type and mutant\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      gene sequences into SH-SY5Y cells to construct a cell model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The present study showed that the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      M139I mutation led to an increase in the A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      \/A\u03b2\n                      <jats:sub>40<\/jats:sub>\n                      ratio. In addition, this mutation induced the expression of \u03b2-site APP-cleaving enzyme 1 (BACE-1). Analysis of the steady-state mechanism showed that the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      M139I mutation cells were more susceptible to endoplasmic reticulum stress and apoptosis under hydrogen peroxide induction than the wild type cells were.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this study, we demonstrate that the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      M139I nucleotide mutation a new mutation that, can increase the ratio of intracellular A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      and A\u03b2\n                      <jats:sub>42<\/jats:sub>\n                      \/A\u03b2\n                      <jats:sub>40,<\/jats:sub>\n                      and increase endoplasmic reticulum stress to promote apoptosis. This supports that the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      M139I mutation is a pathological mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261418314","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T08:50:32Z","timestamp":1771404632000},"page":"909-921","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel presenilin 1 nucleotide mutation (M139I) and its pathological function in a Chinese family with early-onset Alzheimer\u2019s disease"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0840-1346","authenticated-orcid":false,"given":"Xuening","family":"Li","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of the Qingdao University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yameng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Hospital of the Qingdao Binhai University, Qingdao, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyan","family":"Shi","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of the Qingdao University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dacheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhi","family":"Yang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of the Qingdao University"},{"name":"The Affiliated Hospital of the Qingdao University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aijun","family":"Ma","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of the Qingdao University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.12.024"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.disamonth.2010.06.001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.2.168"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2011.221"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.7.7.887"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638622"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2003.39"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1619574114"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608332104"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-010-0233-5"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-020-00232-x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1208"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.3.491"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom15070955"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.010"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.2174\/157015910790909520"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-140-8-200404200-00047"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.741"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23738"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07519.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113613"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.211"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21104"},{"key":"e_1_3_3_29_2","first-page":"247","article-title":"ER-stress in Alzheimer's disease: turning the scale?","volume":"2","author":"Endres K","year":"2013","unstructured":"Endres K, Reinhardt S. 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