iPSCs-derived nerve-like cells from familial Alzheimer's disease PSEN 1 E280A reveal increased amyloid-beta levels and loss of the Y chromosome.
iPSCs-derived nerve-like cells from familial Alzheimer's disease PSEN 1 E280A reveal increased amyloid-beta levels and loss of the Y chromosome.
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DOI：
10.1016/j.neulet.2019.03.032
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发表时间：
2019-06-11
影响因子：
2.5
通讯作者：
Jimenez-Del-Rio M
中科院分区：
文献类型：
--
作者：
Mendivil-Perez M;Velez-Pardo C;Kosik KS;Lopera F;Jimenez-Del-Rio M
阿尔茨海默病（AD）是一种进行性、退行性疾病，主要导致记忆丧失和认知障碍。虽然阿尔茨海默病的病因尚不清楚，但一小部分阿尔茨海默病病例是由早老素-1 （PSEN1）基因突变引起的。诱导多能干细胞（iPSCs）分化的神经细胞可以在体外重现AD的关键病理特征；然而，针对p.E280 A突变的iPSCs研究尚未开展，该突变影响着世界上最大的家族性阿尔茨海默病。尽管有报道称外周血细胞Y染色体缺失与AD风险之间存在联系，但在PSEN1 e280a携带者中尚未对Y染色体相关表型进行研究。在这里，我们报道了将PSEN1 E280 a突变的家族性AD患者的成纤维细胞重编程为iPSCs，然后将神经元分化为神经前体细胞（NPCs），并将NPCs分化为缺乏Y染色体的分化神经元。虽然成功获得了PSEN1 E280 A的iPSCs和npc，但在分化8天后，PSEN1 E280 A分化的神经元通过释放和/或激活死亡标志物大量死亡，与PSEN1野生型细胞相比，未能达到完全的神经分化。
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.
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DOI：
10.1016/s1474-4422(12)70227-2
发表时间：
2012-12
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Fleisher AS;Chen K;Quiroz YT;Jakimovich LJ;Gomez MG;Langois CM;Langbaum JB;Ayutyanont N;Roontiva A;Thiyyagura P;Lee W;Mo H;Lopez L;Moreno S;Acosta-Baena N;Giraldo M;Garcia G;Reiman RA;Huentelman MJ;Kosik KS;Tariot PN;Lopera F;Reiman EM
通讯作者：
Reiman EM
影响因子：
12.3
作者：
Zuo E;Huo X;Yao X;Hu X;Sun Y;Yin J;He B;Wang X;Shi L;Ping J;Wei Y;Ying W;Wei W;Liu W;Tang C;Li Y;Hu J;Yang H
通讯作者：
Yang H
影响因子：
6.4
作者：
Sedlackova T;Repiska G;Celec P;Szemes T;Minarik G
通讯作者：
Minarik G
影响因子：
29
作者：
Quiroz, Yakeel T.;Sperling, Reisa A.;Johnson, Keith A.
通讯作者：
Johnson, Keith A.
影响因子：
9.8
作者：
Dumanski JP;Lambert JC;Rasi C;Giedraitis V;Davies H;Grenier-Boley B;Lindgren CM;Campion D;Dufouil C;European Alzheimer’s Disease Initiative Investigators;Pasquier F;Amouyel P;Lannfelt L;Ingelsson M;Kilander L;Lind L;Forsberg LA
通讯作者：
Forsberg LA