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Cerebral organoids derived from patients with Alzheimer´s disease with PSEN1/2 mutations have defective tissue patterning and altered development

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VÁŇOVÁ Tereza SEDMÍK Jiří RAŠKA Jan AMRUZ ČERNÁ Kateřina TAUŠ Petr POSPÍŠILOVÁ Veronika NEZVEDOVÁ Markéta FEDOROVÁ Veronika KADÁKOVÁ Soňa KLÍMOVÁ Hana CAPANDOVÁ Michaela ORVISKÁ Petra FOJTÍK Petr BÁRTOVÁ Simona PLEVOVÁ Karla SPÁČIL Zdeněk HŘÍBKOVÁ Hana BOHAČIAKOVÁ Dáša

Rok publikování 2023
Druh Článek v odborném periodiku
Časopis / Zdroj CELL REPORTS
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www https://www.sciencedirect.com/science/article/pii/S2211124723013220?via%3Dihub
Doi http://dx.doi.org/10.1016/j.celrep.2023.113310
Klíčová slova Cerebral organoids; Alzheimer's disease; PSEN1/2 mutations
Přiložené soubory
Popis During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study human neural development and disease. Especially in the field of Alzheimer’s disease (AD), remarkable effort has been put into investigating molecular mechanisms behind this disease. Then, with the advent of 3D neuronal cultures and cerebral organoids (COs), several studies have demonstrated that this model can adequately mimic familial and sporadic AD. Therefore, we created an AD-CO model using iPSCs derived from patients with familial AD forms and explored early events and the progression of AD pathogenesis. Our study demonstrated that COs derived from three AD-iPSC lines with PSEN1(A246E) or PSEN2(N141I) mutations developed the AD-specific markers in vitro, yet they also uncover tissue patterning defects and altered development. These findings are complemented by single-cell sequencing data confirming this observation and uncovering that neurons in AD-COs likely differentiate prematurely.
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