{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:34:50Z","timestamp":1774312490632,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102018M3C7A1056894"],"award-info":[{"award-number":["NRF\u20102018M3C7A1056894"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Alzheimer's disease (AD) is the most common neurodegenerative disease which is characterized by the formation of amyloid beta (A\u03b2) plaques and neurofibrillary tangles. These abnormal proteins induce disturbance in mitochondrial dynamics and defect in autophagy system. Since presenilin\u20101 (PS1) is a core component in \u03b3\u2010secretase complex, the mutations of PS1 gene cause the interference of \u03b3\u2010secretase activity and lead to the increased A\u03b2<jats:sub>42<\/jats:sub> secretion. We aimed to characterize the patient\u2010specific induced pluripotent stem cell (iPSC) line carrying PS1\u2010S170F mutation. Furthermore, we tested whether disease\u2010modifying drug can reduce AD pathology in the AD iPSC\u2010derived neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Mononuclear cells (MNCs) were isolated freshly from the peripheral blood of an autosomal dominant AD (ADAD) patient carrying presenilin\u20101 (PS1) mutation (Ser170Phe; PS1\u2010S170F) and a cognitively normal control. We generated induced pluripotent stem cell (iPSC) lines, which were differentiated into functional cortical neurons. Then, we measured the markers indicative of AD pathogenesis using immunocytochemistry and Western blot. We also investigated the mitochondrial dynamics in the AD iPSC\u2010derived neurons using Mito\u2010tracker.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that both extracellular and intracellular A\u03b2 levels were dramatically increased in the PS1\u2010S170F iPSC\u2010derived neurons, compared with the control iPSC\u2010derived neurons. Furthermore, PS1\u2010S170F iPSC\u2010derived neurons showed high expression levels of <jats:italic>p<\/jats:italic>\u2010Tau, which were detected both in the soma and neurites. The mitochondrial velocity in the PS1\u2010S170F iPSC\u2010derived neurons was much reduced, compared with that of the control. We also found a significant decrease of fusion\u2010related protein Mfn1 (membrane proteins mitofusin 1) and an increase of fission\u2010related protein DRP1 (dynamin\u2010related protein 1) in the PS1\u2010S170F iPSC\u2010derived neurons. We further observed the defects of autophagy\u2010related clearance in the PS1\u2010S170F iPSC\u2010derived neurons. Finally, we demonstrated the levels of A\u03b2 and <jats:italic>p<\/jats:italic>\u2010Tau can be dramatically reduced by the treatment of LY\u20102886721, a BACE1 inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, we have established and characterized the pathological features of an AD patient carrying PS1\u2010S170F mutation using iPSC technology, which will be the first case on this mutation and this iPSC line will serve as a useful resource for studying AD pathogenesis and drug screening in the future.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12798","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:50:14Z","timestamp":1585183814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pathological manifestation of the induced pluripotent stem cell\u2010derived cortical neurons from an early\u2010onset Alzheimer's disease patient carrying a presenilin\u20101 mutation (S170F)"],"prefix":"10.1111","volume":"53","author":[{"given":"Ling","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroscience Center Samsung Medical Center Seoul Korea"},{"name":"Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"},{"name":"Samsung Alzheimer Research Center Samsung Medical Center Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jee Hoon","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"},{"name":"Department of Neurology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minchul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonyoung","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Younghoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyohoon","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaehoon","family":"Chung","sequence":"additional","affiliation":[{"name":"Neuroscience Center Samsung Medical Center Seoul Korea"},{"name":"Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"},{"name":"Samsung Alzheimer Research Center Samsung Medical Center Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahito","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"TOKIWA\u2010Bio, Inc. Tsukuba Center Inc. (TCI) Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taeyoung","family":"Yoon","sequence":"additional","affiliation":[{"name":"Dong\u2010A Socio R&amp;D Center Dong\u2010A ST Yongin\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Pyo","family":"Hong","sequence":"additional","affiliation":[{"name":"Theragen Etex Bio Institute Suwon\u2010si Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Won","family":"Seo","sequence":"additional","affiliation":[{"name":"Neuroscience Center Samsung Medical Center Seoul Korea"},{"name":"Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"},{"name":"Center for Clinical Epidemiology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"},{"name":"Department of Health Sciences and Technology SAIHST Sungkyunkwan University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duk L.","family":"Na","sequence":"additional","affiliation":[{"name":"Neuroscience Center Samsung Medical Center Seoul Korea"},{"name":"Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea"},{"name":"Department of Health Sciences and Technology SAIHST Sungkyunkwan University Seoul Korea"},{"name":"Stem Cell &amp; Regenerative Medicine Institute Samsung Medical Center Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6597-8208","authenticated-orcid":false,"given":"Jihwan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA Stem Cell Institute CHA University Seongnam\u2010si Korea"},{"name":"iPS Bio, Inc. 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