{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:27:40Z","timestamp":1772252860599,"version":"3.50.1"},"reference-count":102,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Programme","award":["305299"],"award-info":[{"award-number":["305299"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genes associated with immune response and inflammation have been identified as genetic risk factors for late-onset Alzheimer\u00b4s disease (LOAD). The rare R47H variant within triggering receptor expressed on myeloid cells 2 (TREM2) has been shown to increase the risk for developing Alzheimer\u2019s disease (AD) 2\u20133-fold. Here, we report the generation and characterization of a model of late-onset Alzheimer\u2019s disease (LOAD) using lymphoblast-derived induced pluripotent stem cells (iPSCs) from patients carrying the TREM2 R47H mutation, as well as from control individuals without dementia. All iPSCs efficiently differentiated into mature neuronal cultures, however AD neuronal cultures showed a distinct gene expression profile. Furthermore, manipulation of the iPSC-derived neuronal cultures with an A\u03b2-S8C dimer highlighted metabolic pathways, phagosome and immune response as the most perturbed pathways in AD neuronal cultures. Through the construction of an A\u03b2-induced gene regulatory network, we were able to identify an A\u03b2 signature linked to protein processing in the endoplasmic reticulum (ER), which emphasized ER-stress, as a potential causal role in LOAD. Overall, this study has shown that our AD-iPSC based model can be used for in-depth studies to better understand the molecular mechanisms underlying the etiology of LOAD and provides new opportunities for screening of potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms21124516","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:36:54Z","timestamp":1593081414000},"page":"4516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["IPSC-Derived Neuronal Cultures Carrying the Alzheimer\u2019s Disease Associated TREM2 R47H Variant Enables the Construction of an A\u03b2-Induced Gene Regulatory Network"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7894-6539","authenticated-orcid":false,"given":"Soraia","family":"Martins","sequence":"first","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"M\u00fcller-Schiffmann","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Erichsen","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Bohndorf","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9153-7051","authenticated-orcid":false,"given":"Wasco","family":"Wruck","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristel","family":"Sleegers","sequence":"additional","affiliation":[{"name":"Neurodegenerative Brain Diseases Group, VIB-Center for Molecular Neurology, University of Antwerp, 20610 Antwerp, Belgium"},{"name":"Department of Biomedical Sciences, University of Antwerp, 20610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-7665","authenticated-orcid":false,"given":"Christine","family":"Van Broeckhoven","sequence":"additional","affiliation":[{"name":"Neurodegenerative Brain Diseases Group, VIB-Center for Molecular Neurology, University of Antwerp, 20610 Antwerp, Belgium"},{"name":"Department of Biomedical Sciences, University of Antwerp, 20610 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Korth","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-6761","authenticated-orcid":false,"given":"James","family":"Adjaye","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"ref_1","unstructured":"Patterson, C. 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