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induced pluripotent stem cell alzheimer's

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https://www.readbyqxmd.com/read/27897204/human-mitochondrial-transcriptional-factor-a-breaks-the-mitochondria-mediated-vicious-cycle-in-alzheimer-s-disease
#1
Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu
In the mitochondria-mediated vicious cycle of Alzheimer's disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA)...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879212/generation-of-a-gene-corrected-isogenic-control-cell-line-from-an-alzheimer-s-disease-patient-ipsc-line-carrying-a-a79v-mutation-in-psen1
#2
Carlota Pires, Benjamin Schmid, Carina Petræus, Anna Poon, Natakarn Nimsanor, Troels T Nielsen, Gunhild Waldemar, Lena E Hjermind, Jørgen E Nielsen, Poul Hyttel, Kristine K Freude
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease causing neural cell degeneration and brain atrophy and is considered to be the most common form of dementia. We previously generated an induced pluripotent stem cell (iPSC) line from an AD patient carrying an A79V mutation in PSEN1 as an in vitro disease model. Here we generated a gene-corrected version from this hiPSC line by substituting the point mutation with the wild-type sequence. The reported A79V-GC-iPSCs line is a very useful resource in combination with the A79V-iPSC line in order to study pathological cellular phenotypes related to this particular mutation...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27853631/stepping-back-to-move-forward-a-current-review-of-ipscs-in-the-fight-against-alzheimer-s-disease
#3
REVIEW
Aditya Devineni, Scarlett Tohme, Michael T Kody, R Adams Cowley, Brent T Harris
The successful generation of the first iPSCs about ten years ago has provided deeper insight into previously unknown disease mechanisms and therapeutic opportunities for many diseases. In particular, iPSCs are becoming an important tool in advancing modeling and therapeutic intervention for Alzheimer's disease. In this manuscript, we assess the research climate surrounding the application of iPSCs to familial and sporadic Alzheimer's disease, including the generation and isolation of individualized neural stem cells, the introduction of neural stem cell transplants using iPSCs, and an estimation of the potential use of iPSCs as research models for Alzheimer's treatments and therapies...
2016: American Journal of Stem Cells
https://www.readbyqxmd.com/read/27819315/sustained-synchronized-neuronal-network-activity-in-a-human-astrocyte-co-culture-system
#4
Jacobine Kuijlaars, Tutu Oyelami, Annick Diels, Jutta Rohrbacher, Sofie Versweyveld, Giulia Meneghello, Marianne Tuefferd, Peter Verstraelen, Jan R Detrez, Marlies Verschuuren, Winnok H De Vos, Theo Meert, Pieter J Peeters, Miroslav Cik, Rony Nuydens, Bert Brône, An Verheyen
Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27789410/lymphoblast-derived-integration-free-ipsc-lines-from-a-female-and-male-alzheimer-s-disease-patient-expressing-different-copy-numbers-of-a-coding-cnv-in-the-alzheimer-risk-gene-cr1
#5
Friederike Schröter, Kristel Sleegers, Caroline Van Cauwenberghe, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female and male patient diagnosed with Alzheimer's disease (AD) with different genotypes of a functional copy number variation (CNV) in the AD risk gene CR1 were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the CR1 CNV, and comparative transcriptome analyses with the human embryonic stem cell line H1 revealed a Pearson correlation of 0.956 for AD1-CR10 and 0...
October 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789408/lymphoblast-derived-integration-free-ips-cell-line-from-a-female-67-year-old-alzheimer-s-disease-patient-with-trem2-r47h-missense-mutation
#6
Friederike Schröter, Kristel Sleegers, Elise Cuyvers, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female patient diagnosed with Alzheimer's disease (AD) possessing the missense mutation TREM2 p.R47H were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the TREM2 mutation, and were defined as pluripotent based on (i) expression of pluripotent-associated markers, (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptomes of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
October 20, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789396/derivation-of-induced-pluripotent-stem-cells-from-a-familial-alzheimer-s-disease-patient-carrying-the-l282f-mutation-in-presenilin-1
#7
Anna Poon, Tong Li, Carlota Pires, Troels T Nielsen, Jørgen E Nielsen, Bjørn Holst, Andras Dinnyes, Poul Hyttel, Kristine K Freude
Mutations in presenilin 1 (PSEN1) lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients can be differentiated and used for disease modeling. Here, we derived hiPSC from skin fibroblasts obtained from an AD patient carrying a L282F mutation in PSEN1. We transfected skin fibroblasts with episomal iPSC reprogramming vectors targeting human OCT4, SOX2, L-MYC, KLF4, NANOG, LIN28, and short hairpin RNA against TP53. Our hiPSC line, L282F-hiPSC, displayed typical stem cell characteristics with consistent expression of pluripotency genes and the ability to differentiation into the three germ layers...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789395/generation-of-a-gene-corrected-isogenic-control-hipsc-line-derived-from-a-familial-alzheimer-s-disease-patient-carrying-a-l150p-mutation-in-presenilin-1
#8
Anna Poon, Benjamin Schmid, Carlota Pires, Troels T Nielsen, Lena E Hjermind, Jørgen E Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude
Mutations in the presenilin 1 (PSEN1) gene lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients and subsequently differentiated can be used for disease modeling. We have previously generated a hiPSC line from a familial AD patient carrying a L150P point mutation in PSEN1. Here we used CRISPR/Cas9 gene editing to correct for the single base pair mutation. This gene-corrected line, L150P-GC-hiPSC, serves as an isogenic control to the mutant line for future investigation of mechanisms and cellular phenotypes altered by this specific PSEN1 mutation...
September 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27762639/stem-cells-for-modeling-and-therapy-of-parkinson-s-disease
#9
Qingxi Zhang, Wanling Chen, Sheng Tan, Tongxiang Lin
Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, which is characterized by low level of dopamine expressing in the striatum and deteriorated dopaminergic neurons (DAn) in Substantia nigra pars compacta (SNpc). Generation of PD-derived DAn including differentiation of human embryonic stem cell (hESC), human neural stem cell (hNSC), human induced pluripotent stem cell (hiPSC) and directly reprogramming provide an ideal tool to model PD, which created the possibilities of mimicking key essential pathological processes charactering single cell changes in vitro...
October 20, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27725795/astrocyte-differentiation-of-human-pluripotent-stem-cells-new-tools-for-neurological-disorder-research
#10
Abinaya Chandrasekaran, Hasan X Avci, Marcel Leist, Julianna Kobolák, Andras Dinnyés
Astrocytes have a central role in brain development and function, and so have gained increasing attention over the past two decades. Consequently, our knowledge about their origin, differentiation and function has increased significantly, with new research showing that astrocytes cultured alone or co-cultured with neurons have the potential to improve our understanding of various central nervous system diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease, or Alexander disease. The generation of astrocytes derived from pluripotent stem cells (PSCs) opens up a new area for studying neurologic diseases in vitro; these models could be exploited to identify and validate potential drugs by detecting adverse effects in the early stages of drug development...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27720902/targeted-differentiation-of-regional-ventral-neuroprogenitors-and-related-neuronal-subtypes-from-human-pluripotent-stem-cells
#11
Liankai Chi, Beibei Fan, Kunshan Zhang, Yanhua Du, Zhongliang Liu, Yujiang Fang, Zhenyu Chen, Xudong Ren, Xiangjie Xu, Cizhong Jiang, Siguang Li, Lin Ma, Liang Gao, Ling Liu, Xiaoqing Zhang
Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27693548/toward-personalized-intervention-for-alzheimer-s-disease
#12
Xing Peng, Peiqi Xing, Xiuhui Li, Ying Qian, Fuhai Song, Zhouxian Bai, Guangchun Han, Hongxing Lei
Alzheimer's disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells (iPSCs)...
September 28, 2016: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/27684569/three-dimensional-human-neuro-spheroid-model-of-alzheimer-s-disease-based-on-differentiated-induced-pluripotent-stem-cells
#13
Han-Kyu Lee, Clara Velazquez Sanchez, Mei Chen, Peter J Morin, John M Wells, Eugene B Hanlon, Weiming Xia
The testing of candidate drugs to slow progression of Alzheimer's disease (AD) requires clinical trials that are lengthy and expensive. Efforts to model the biochemical milieu of the AD brain may be greatly facilitated by combining two cutting edge technologies to generate three-dimensional (3D) human neuro-spheroid from induced pluripotent stem cells (iPSC) derived from AD subjects. We created iPSC from blood cells of five AD patients and differentiated them into 3D human neuronal culture. We characterized neuronal markers of our 3D neurons by immunocytochemical staining to validate the differentiation status...
2016: PloS One
https://www.readbyqxmd.com/read/27668937/efficient-derivation-of-microglia-like-cells-from-human-pluripotent-stem-cells
#14
Julien Muffat, Yun Li, Bingbing Yuan, Maisam Mitalipova, Attya Omer, Sean Corcoran, Grisilda Bakiasi, Li-Huei Tsai, Patrick Aubourg, Richard M Ransohoff, Rudolf Jaenisch
Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions...
November 2016: Nature Medicine
https://www.readbyqxmd.com/read/27622770/self-organizing-3d-human-neural-tissue-derived-from-induced-pluripotent-stem-cells-recapitulate-alzheimer-s-disease-phenotypes
#15
Waseem K Raja, Alison E Mungenast, Yuan-Ta Lin, Tak Ko, Fatema Abdurrob, Jinsoo Seo, Li-Huei Tsai
The dismal success rate of clinical trials for Alzheimer's disease (AD) motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cells (iPSCs) allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe...
2016: PloS One
https://www.readbyqxmd.com/read/27616476/improving-and-accelerating-the-differentiation-and-functional-maturation-of-human-stem-cell-derived-neurons-role-of-extracellular-calcium-and-gaba
#16
Paul J Kemp, David J Rushton, Polina L Yarova, Christian Schnell, Charlene Geater, Jane M Hancock, Annalena Wieland, Alis Hughes, Luned Badder, Emma Cope, Daniela Riccardi, Andrew D Randall, Jonathan T Brown, Nicholas D Allen, Vsevolod Telezhkin
Neurons differentiated from pluripotent stem cells using established neural culture conditions often exhibit functional deficits. Recently, we have developed enhanced media which both synchronize the neurogenesis of pluripotent stem cell-derived neural progenitors and accelerate their functional maturation; together these media are termed SynaptoJuice. This pair of media are pro-synaptogenic and generate authentic, mature synaptic networks of connected forebrain neurons from a variety of induced pluripotent and embryonic stem cell lines...
November 15, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27589520/specific-triazine-herbicides-induce-amyloid-%C3%AE-42-production
#17
Erik Portelius, Emilie Durieu, Marion Bodin, Morgane Cam, Josef Pannee, Charlotte Leuxe, Aloϊse Mabondzo, Nassima Oumata, Hervé Galons, Jung Yeol Lee, Young-Tae Chang, Kathrin Stϋber, Philipp Koch, Gaëlle Fontaine, Marie-Claude Potier, Antigoni Manousopoulou, Spiros D Garbis, Adrian Covaci, Debby Van Dam, Peter De Deyn, Frank Karg, Marc Flajolet, Chiori Omori, Saori Hata, Toshiharu Suzuki, Kaj Blennow, Henrik Zetterberg, Laurent Meijer
Proteolytic cleavage of the amyloid-β protein precursor (AβPP) by secretases leads to extracellular release of amyloid-β (Aβ) peptides. Increased production of Aβ42 over Aβ40 and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark. Identifying products of the 'human chemical exposome' (HCE) able to induce Aβ42 production may be a key to understanding some of the initiating causes of AD and to generate non-genetic, chemically-induced AD animal models. A cell model was used to screen HCE libraries for Aβ42 inducers...
October 18, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27558608/establishment-of-induced-pluripotent-stem-cell-ipsc-line-from-a-75-year-old-patient-with-late-onset-alzheimer-s-disease-load
#18
Zsuzsanna Táncos, Eszter Varga, Eszter Kovács, András Dinnyés, Julianna Kobolák
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 75-year old woman with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies...
May 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27558607/establishment-of-induced-pluripotent-stem-cell-ipsc-line-from-a-63-year-old-patient-with-late-onset-alzheimer-s-disease-load
#19
Abinaya Chandrasekaran, Eszter Varga, Csilla Nemes, Zsuzsanna Táncos, Julianna Kobolák, András Dinnyés
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 63-year old woman with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies...
May 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27558606/establishment-of-induced-pluripotent-stem-cell-ipsc-line-from-an-84-year-old-patient-with-late-onset-alzheimer-s-disease-load
#20
Zsuzsanna Táncos, Eszter Varga, Eszter Kovács, András Dinnyés, Julianna Kobolák
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically characterised 84-year old male with late onset Alzheimer's disease (LOAD). The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus delivery system. The transgene-free iPSC showed pluripotency verified by immunocytochemistry for pluripotency markers and differentiated spontaneously towards the 3 germ layers in vitro. Furthermore, the iPSC line showed normal karyotype. Our model might offer a good platform to further study the pathomechanism of sporadic AD, to identify early biomarkers and also for drug testing and gene therapy studies...
May 24, 2016: Stem Cell Research
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