Neurons Derived from Induced Pluripotent Stem Cells of Patients with Down Syndrome Reproduce Early Stages of Alzheimer's Disease Type Pathology in vitro

被引：24

作者：

Dashinimaev, Erdem B. ^{[1
,2
]}

Artyuhov, Alexander S. ^{[2
]}

Bolshakov, Alexey P. ^{[3
]}

Vorotelyak, Ekaterina A. ^{[1
,2
,4
,5
]}

Vasiliev, Andrey V. ^{[1
,5
]}

机构：

[1] Russian Acad Sci, Koltzov Inst Dev Biol IDB, Vavilova Str 26, Moscow 119334, Russia

[2] Pirogov Russian Natl Res Med Univ, Moscow, Russia

[3] Russian Acad Sci, Inst Higher Nervous Act & Neurophysiol, Moscow, Russia

[4] State Univ, Moscow Inst Phys & Technol, Dolgoprudnyi, Russia

[5] Lomonosov Moscow State Univ, Moscow, Russia

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2017年 / 56卷 / 02期

关键词：

Alzheimer's disease; amyloid-beta; A beta(42); APP; BACE2; Down syndrome; ETS2; IPSC; RCAN1; TMED10; AMYLOID-BETA-PEPTIDES; CHROMOSOME; 21; EXPRESSION; PROTEINS;

D O I：

10.3233/JAD-160945

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid- (A beta) manifested by increased secretion and accumulation of A beta granules of A beta(42) pathological isoform with upregulated expression of the APP gene. Additionally, we found increased expression levels of genes that are considered to be associated with AD (BACE2, RCAN1, ETS2, TMED10), as compared to healthy controls. Thus, the neural cells generated from induced pluripotent stem cells with DS reproduce initial cellular signs of AD- type pathology and can be useful tools for modeling and studying this variant of AD in vitro.

引用

页码：835 / 847

页数：13

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