{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:51:48Z","timestamp":1762782708731,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"6","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\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A6A1A03038996"],"award-info":[{"award-number":["2021R1A6A1A03038996"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VHS Medical Center research grant","award":["VHSM21023"],"award-info":[{"award-number":["VHSM21023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early-onset Alzheimer\u2019s disease (EOAD) is characterized by the presence of neurological symptoms in patients with Alzheimer\u2019s disease (AD) before 65 years of age. Mutations in pathological genes, including amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), were associated with EOAD. Seventy-six mutations in PSEN2 have been found around the world, which could affect the activity of \u03b3-secretase in amyloid beta processing. Here, a heterozygous PSEN2 point mutation from G to A nucleotide change at position 166 (codon 56; c.166G&gt;A, Gly56Ser) was identified in a 64-year-old Korean female with AD with progressive cognitive memory impairment for the 4 years prior to the hospital visit. Hippocampal atrophy was observed from magnetic resonance imaging-based neuroimaging analyses. Temporal and parietal cortex hypometabolisms were identified using fluorodeoxyglucose positron emission tomography. This mutation was at the N-terminal portion of the presenilin 2 protein on the cytosolic side. Therefore, the serine substitution may have promoted AD pathogenesis by perturbing to the mutation region through altered phosphorylation of presenilin. In silico analysis revealed that the mutation altered protein bulkiness with increased hydrophilicity and reduced flexibility of the mutated region of the protein. Structural changes were likely caused by intramolecular interactions between serine and other residues, which may have affected APP processing. The functional study will clarify the pathogenicity of the mutation in the future.<\/jats:p>","DOI":"10.3390\/ijms23062967","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:30:38Z","timestamp":1646825438000},"page":"2967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Possible Pathogenic PSEN2 Gly56Ser Mutation in a Korean Patient with Early-Onset Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Kyu-Hwan","family":"Shim","sequence":"first","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam-si 13120, 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 Health Service Medical Center, Veterans Medical Research Institute, Seoul 05368, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heewon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Neurology, Veterans Health Service Medical Center, Veterans Medical Research Institute, Seoul 05368, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam-si 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8123-6183","authenticated-orcid":false,"given":"Seong-Soo","family":"An","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology, Gachon University, Seongnam-si 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-9707","authenticated-orcid":false,"given":"Da-Eun","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Veterans Health Service Medical Center, Veterans Medical Research Institute, Seoul 05368, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3389\/fnagi.2018.00359","article-title":"The Early Events That Initiate \u03b2-Amyloid Aggregation in Alzheimer\u2019s Disease","volume":"10","author":"Zhang","year":"2018","journal-title":"Front. 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