iPSCs-derived nerve-like cells from familial Alzheimer's disease PSEN 1 E280A reveal increased amyloid-beta levels and loss of the Y chromosome

NEUROSCIENCE LETTERS

卷:703

Article

Mendivil-Perez, Miguel¹  Velez-Pardo, Carlos¹  Kosik, Kenneth S.²  Lopera, Francisco¹  Jimenez-Del-Rio, Marlene¹ 

[1] Univ Antioquia UdeA, Fac Med, Med Res Inst, Neurosci Res Grp, Calle 70 52-21 & Calle 62 52-59,Bldg 1,Room 412, Siu Medellin, Colombia

[2] Univ Calif Santa Barbara, Neurosci Res Inst, Dept Mol Cellular Dev Biol, Santa Barbara, CA 93106 USA

关键词: Familial Alzheimer disease;    Chromosome Y;    E280A;    iPSCs;    PSEN1;   

DOI  :  10.1016/j.neulet.2019.03.032

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) is a progressive, degenerative disorder that mainly results in memory loss and a cognitive disorder. Although the cause of AD is still unknown, a minor percentage of AD cases are produced by genetic mutations in the presenilin-1 (PSEN1) gene. Differentiated neuronal cells derived from induced pluripotent stem cells (iPSCs) of patients can recapitulate key pathological features of AD in vitro; however, iPSCs studies focused on the p.E280 A mutation, which afflicts the largest family in the world with familial AD, have not been carried out yet. Although a link between the loss of the Y (LOY) chromosome in peripheral blood cells and risk for AD has been reported, LOY-associated phenotype has not been previously studied in PSEN1 E280 A carriers. Here, we report the reprogramming of fibroblast cells into iPSCs from a familial AD patient with the PSEN1 E280 A mutation, followed by neuronal differentiation into neural precursor cells (NPCs), and the differentiation of NPCs into differentiated neurons that lacked a Y chromosome. Although the PSEN1 E280 A iPSCs and NPCs were successfully obtained, after 8 days of differentiation, PSEN1 E280 A differentiated neurons massively died reflected by release and/ or activation of death markers, and failed to reach complete neural differentiation compared to PSEN 1 wild type cells.

【 授权许可】

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