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Using cerebral organoids derived from human-induced pluripotent stem cells (hiPSCs) carrying the familial\n                    <jats:italic>PSEN1<\/jats:italic>\n                    A246E variant, we investigated the temporal relationship between amyloid-\u03b2 (A\u03b2) dysregulation and spontaneous neuronal activity. Multielectrode array recordings from the differentiation day 60 (DD60) to at least DD130 revealed that AD organoids exhibited transient hyperexcitability and hypersynchrony compared with wild-type (WT) controls, followed by a gradual decline in activity. During the enhanced excitability stage, both elevated A\u03b242\/40 and A\u03b2 aggregate size showed positive correlations with the percentage of active electrodes and the global synchrony index (GSI) in AD organoids. These findings indicate that A\u03b2 dysregulation might contribute to transient network hyperexcitability in early AD. The results also suggest that patient-derived cerebral organoids may serve as a translational model to examine early network dysfunction and inform future investigations of potential A\u03b2-induced changes in excitability during the preclinical stages of AD.\n                  <\/jats:p>","DOI":"10.1007\/s10571-026-01779-7","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T18:53:27Z","timestamp":1784573607000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patient-Derived PSEN1 Cerebral Organoids Revealed Parallel Development of Amyloid-\u03b2 Accumulation and Network Dysfunction"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1034-1144","authenticated-orcid":false,"given":"Andrijana","family":"Angelovski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-7085","authenticated-orcid":false,"given":"Hana","family":"Hribkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-1061","authenticated-orcid":false,"given":"Jiri","family":"Sedmik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4947-0242","authenticated-orcid":false,"given":"Barbora","family":"Liscakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3946-3531","authenticated-orcid":false,"given":"Olga","family":"Svecova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-6207","authenticated-orcid":false,"given":"Sona","family":"Cesnarikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-0402","authenticated-orcid":false,"given":"Katerina","family":"Amruz Cerna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-678X","authenticated-orcid":false,"given":"Veronika","family":"Pospisilova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3872-2742","authenticated-orcid":false,"given":"Martin","family":"Kral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1785-683X","authenticated-orcid":false,"given":"Martina","family":"Kolajova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-9518","authenticated-orcid":false,"given":"Petr","family":"Klimes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9538-6668","authenticated-orcid":false,"given":"Dasa","family":"Bohaciakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2674-1846","authenticated-orcid":false,"given":"Marketa","family":"Bebarova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"issue":"4","key":"1779_CR1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaf274","volume":"7","author":"H Abuwarda","year":"2025","unstructured":"Abuwarda H, Trainer A, Horien C, Shen X, Moret S, Ju S, Constable RT, Fredericks C (2025) Whole-brain functional connectivity predicts regional tau PET in preclinical Alzheimer\u2019s disease. 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