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induced pluripotent stem cell alzheimer's

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https://www.readbyqxmd.com/read/29328972/establishment-of-tusmi003-a-an-induced-pluripotent-stem-cell-ipsc-line-from-a-62-year-old-chinese-han-patient-with-alzheimer-s-disease-with-apoe3-4-genetic-background
#1
Ying Wang, Hongxiang Yu, Yue Zhang, Jing Zhang, Keni Chen, Heng Sun, Shulin Meng, Gang Li, Ying Lei, Jian Zhao
A 62-year old Chinese Han Alzheimer's disease (AD) female patient with ApoE3/4 genetic background donated her Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system was used to reprogrammed PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29304399/establishment-of-induced-pluripotent-stem-cell-line-zzui009-a-from-an-alzheimer-s-disease-patient-carrying-a-psen1-gene-mutation
#2
Yanlin Wang, Na Jing, Linlin Su, Changhe Shi, Pei Zhang, Zhilei Wang, Huifang Sun, Jing Yang, Yutao Liu, Xuejun Wen, Jin Zhang, Shoutao Zhang, Yuming Xu
Skin fibroblasts were obtained from a 42-year-old Alzheimer's disease (AD) patient carrying mutations in the PSEN1 gene. An iPSC line was successfully established using the Sendai-virus (SeV) delivery system. The patient-specific iPSCs were free of genomically integrated reprogramming genes, had the specific mutation, expressed the expected pluripotency markers, and had the potential to differentiate into cells of all three germ layers. Our model might offer a robust platform for further study of the pathomechanism of this disease as well as drug testing and gene therapy studies...
December 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29246571/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui003-a-and-non-demented-control-asui004-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#3
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers...
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29191219/neurons-derived-from-sporadic-alzheimer-s-disease-ipscs-reveal-elevated-tau-hyperphosphorylation-increased-amyloid-levels-and-gsk3b-activation
#4
Anna Ochalek, Balázs Mihalik, Hasan X Avci, Abinaya Chandrasekaran, Annamária Téglási, István Bock, Maria Lo Giudice, Zsuzsanna Táncos, Kinga Molnár, Lajos László, Jørgen E Nielsen, Bjørn Holst, Kristine Freude, Poul Hyttel, Julianna Kobolák, András Dinnyés
BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia, affecting one in eight adults over 65 years of age. The majority of AD cases are sporadic, with unknown etiology, and only 5% of all patients with AD present the familial monogenic form of the disease. In the present study, our aim was to establish an in vitro cell model based on patient-specific human neurons to study the pathomechanism of sporadic AD. METHODS: We compared neurons derived from induced pluripotent stem cell (iPSC) lines of patients with early-onset familial Alzheimer's disease (fAD), all caused by mutations in the PSEN1 gene; patients with late-onset sporadic Alzheimer's disease (sAD); and three control individuals without dementia...
December 1, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29156377/establishment-of-induced-pluripotent-stem-cell-line-zzui010-a-from-an-alzheimer-s-disease-patient-carrying-an-app-gene-mutation
#5
Zhilei Wang, Pei Zhang, Yanlin Wang, Changhe Shi, Na Jing, Huifang Sun, Jing Yang, Yutao Liu, Xuejun Wen, Jin Zhang, Shoutao Zhang, Yuming Xu
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Previous studies have identified mutations in several genes, such as amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), in patients with early-onset (<65years) familial AD. Recently, a patient with an APP gene mutation was identified; the dermal fibroblasts of the patient were obtained and a line of induced pluripotent stem cells (iPSCs) was successfully generated using the Sendai-virus (SeV) delivery system...
November 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29153989/psen1-mutant-ipsc-derived-model-reveals-severe-astrocyte-pathology-in-alzheimer-s-disease
#6
Minna Oksanen, Andrew J Petersen, Nikolay Naumenko, Katja Puttonen, Šárka Lehtonen, Max Gubert Olivé, Anastasia Shakirzyanova, Stina Leskelä, Timo Sarajärvi, Matti Viitanen, Juha O Rinne, Mikko Hiltunen, Annakaisa Haapasalo, Rashid Giniatullin, Pasi Tavi, Su-Chun Zhang, Katja M Kanninen, Riikka H Hämäläinen, Jari Koistinaho
Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls...
December 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29151989/human-induced-pluripotent-stem-cells-and-the-modelling-of-alzheimer-s-disease-the-human-brain-outside-the-dish
#7
REVIEW
Godwin Tong, Pablo Izquierdo, Rana Arham Raashid
Background: Neurodegenerative diseases like Alzheimer's Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments. Summary: With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth...
2017: Open Neurology Journal
https://www.readbyqxmd.com/read/29034886/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui001-a-and-non-demented-control-asui002-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#8
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi001-A] and a non-demented control (NDC) patient [ASUi002-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and demonstrated the ability to differentiate into cells representative of the three germ layers...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28992104/a-simplified-and-sensitive-method-to-identify-alzheimer-s-disease-biomarker-candidates-using-patient-derived-induced-pluripotent-stem-cells-ipscs
#9
Keiro Shirotani, Kazuya Matsuo, Sumio Ohtsuki, Takeshi Masuda, Masashi Asai, Yumiko Kutoku, Yutaka Ohsawa, Yoshihide Sunada, Takayuki Kondo, Haruhisa Inoue, Nobuhisa Iwata
We developed a simplified and sensitive method to identify Alzheimer's disease (AD) biomarker candidates by a quantitative and targeted proteomic analysis (combination of liquid chromatography tandem mass spectrometry and multiplexed-multiple reaction monitoring/selected reaction monitoring analysis) of culture media from neurons differentiated from induced pluripotent stem cells (iPSCs) established from AD patients. We found that alpha-1-acid glycoprotein (ORM1) was decreased in the culture media of AD-iPSC-derived neurons, consistent with previous observations for AD patient cerebrospinal fluid, thus validating our new strategy...
September 4, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28969469/using-induced-pluripotent-stem-cells-to-explore-genetic-and-epigenetic-variation-associated-with-alzheimer-s-disease
#10
Jennifer Imm, Talitha L Kerrigan, Aaron Jeffries, Katie Lunnon
It is thought that both genetic and epigenetic variation play a role in Alzheimer's disease initiation and progression. With the advent of somatic cell reprogramming into induced pluripotent stem cells it is now possible to generate patient-derived cells that are able to more accurately model and recapitulate disease. Furthermore, by combining this with recent advances in (epi)genome editing technologies, it is possible to begin to examine the functional consequence of previously nominated genetic variants and infer epigenetic causality from recently identified epigenetic variants...
October 3, 2017: Epigenomics
https://www.readbyqxmd.com/read/28966121/scalable-production-of-ipsc-derived-human-neurons-to-identify-tau-lowering-compounds-by-high-content-screening
#11
Chao Wang, Michael E Ward, Robert Chen, Kai Liu, Tara E Tracy, Xu Chen, Min Xie, Peter Dongmin Sohn, Connor Ludwig, Anke Meyer-Franke, Celeste M Karch, Sheng Ding, Li Gan
Lowering total tau levels is an attractive therapeutic strategy for Alzheimer's disease and other tauopathies. High-throughput screening in neurons derived from human induced pluripotent stem cells (iPSCs) is a powerful tool to identify tau-targeted therapeutics. However, such screens have been hampered by heterogeneous neuronal production, high cost and low yield, and multi-step differentiation procedures. We engineered an isogenic iPSC line that harbors an inducible neurogenin 2 transgene, a transcription factor that rapidly converts iPSCs to neurons, integrated at the AAVS1 locus...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28965985/dysfunctions-of-mitochondria-in-close-association-with-strong-perturbation-of-long-noncoding-rnas-expression-in-down-syndrome
#12
Jia-Jun Qiu, Yan-Na Liu, Zhao-Rui Ren, Jing-Bin Yan
Trisomy 21 is the most common chromosomal disorder and underlies Down syndrome. Epigenetics, such as DNA methylation and post-translational histone modifications, plays a vital role in Down syndrome. However, the functions of epigenetics-related long noncoding RNAs (lncRNAs), found to have an impact on neural diseases such as Alzheimer's disease, remain unknown in Down syndrome. In this study, we analyzed the RNA sequencing data from Down syndrome-induced pluripotent stem cells (iPSCs) and normal iPSCs. A large number of lncRNAs were identified differentially expressed in Down syndrome-iPSCs...
November 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28959184/mitophagy-failure-in-fibroblasts-and-ipsc-derived-neurons-of-alzheimer-s-disease-associated-presenilin-1-mutation
#13
Patricia Martín-Maestro, Ricardo Gargini, Andrew A Sproul, Esther García, Luis C Antón, Scott Noggle, Ottavio Arancio, Jesús Avila, Vega García-Escudero
Familial Alzheimer's disease (FAD) is clearly related with the accumulation of amyloid-beta (Aβ) and its deleterious effect on mitochondrial function is well established. Anomalies in autophagy have also been described in these patients. In the present work, functional analyses have been performed to study mitochondrial recycling process in patient-derived fibroblasts and neurons from induced pluripotent stem cells harboring the presenilin 1 mutation A246E. Mitophagy impairment was observed due to a diminished autophagy degradation phase associated with lysosomal anomalies, thus causing the accumulation of dysfunctional mitochondria labeled by Parkin RBR E3 ubiquitin protein ligase (PARK2)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28912154/inhibition-of-p25-cdk5-attenuates-tauopathy-in-mouse-and-ipsc-models-of-frontotemporal-dementia
#14
Jinsoo Seo, Oleg Kritskiy, L Ashley Watson, Scarlett J Barker, Dilip Dey, Waseem K Raja, Yuan-Ta Lin, Tak Ko, Sukhee Cho, Jay Penney, M Catarina Silva, Steven D Sheridan, Diane Lucente, James F Gusella, Bradford C Dickerson, Stephen J Haggarty, Li-Huei Tsai
Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease. Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double-transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice...
October 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28903069/cell-reprogramming-therapeutic-potential-and-the-promise-of-rejuvenation-for-the-aging-brain
#15
REVIEW
Micaela López-León, Tiago F Outeiro, Rodolfo G Goya
Aging is associated with a progressive increase in the incidence of neurodegenerative diseases, with Alzheimer's (AD) and Parkinson's (PD) disease being the most conspicuous examples. Within this context, the absence of efficacious therapies for most age-related brain pathologies has increased the interest in regenerative medicine. In particular, cell reprogramming technologies have ushered in the era of personalized therapies that not only show a significant potential for the treatment of neurodegenerative diseases but also promise to make biological rejuvenation feasible...
September 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28880277/use-of-a-neonatal-rat-system-as-a-bioincubator-to-generate-adult-like-mature-cardiomyocytes-from-human-and-mouse-pluripotent-stem-cells
#16
Gun-Sik Cho, Emmanouil Tampakakis, Peter Andersen, Chulan Kwon
Pluripotent stem cells (PSCs), including induced PSCs, hold great potential for personalized disease modeling, drug testing and cell-based therapeutics. However, cells differentiated from PSCs remain immature in a dish, and thus there are serious caveats to their use in modeling adult-onset diseases such as cardiomyopathies and Alzheimer's disease. By taking advantage of knowledge gained about mammalian development and from bioinformatics analyses, we recently developed a neonatal rat system that enables maturation of PSC-derived cardiomyocytes into cardiomyocytes analogous to those seen in adult animals...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28822354/3d-brain-organoids-derived-from-pluripotent-stem-cells-promising-experimental-models-for-brain-development-and-neurodegenerative-disorders
#17
REVIEW
Chun-Ting Lee, Raphael M Bendriem, Wells W Wu, Rong-Fong Shen
Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials...
August 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28805182/human-induced-pluripotent-stem-cells-as-a-research-tool-in-alzheimer-s-disease
#18
J P Robbins, J Price
Human-induced pluripotent stem cells (iPSCs) offer a novel, timely approach for investigating the aetiology of neuropsychiatric disorders. Although we are starting to gain more insight into the specific mechanisms that cause Alzheimer's disease and other forms of dementia, this has not resulted in therapies to slow the pathological processes. Animal models have been paramount in studying the neurobiological processes underlying psychiatric disorders. Nonetheless, these human conditions cannot be entirely recapitulated in rodents...
November 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28748763/induced-pluripotent-stem-cell-technology-a-paradigm-shift-in-medical-science-for-drug-screening-and-disease-modeling
#19
Meera Nair, Sardul Singh Sandhu, Anil Kumar Sharma
BACKGROUND: Induced Pluripotent Stem Cell (IPSC) Technology is the most advanced research as it offers an attractive alternative for establishing patient-specific IPSCs to recapitulate phenotypes of not only monogenic diseases (viz. Thalassaemia, Sickle cell anemia, Haemophilia, Tay-Sachs disease), but also late-onset polygenic diseases (viz. Parkinson's disease, Alzheimer's disease, schizophrenia). Over the hindsight, numerous studies of the past and current scientists have led to the production, maturation and understanding of induced pluripotent stem cell technology and its use in basic and clinical research...
July 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28696436/reduced-trpc6-mrna-levels-in-the-blood-cells-of-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment
#20
R Lu, J Wang, R Tao, J Wang, T Zhu, W Guo, Y Sun, H Li, Y Gao, W Zhang, C J Fowler, Q Li, S Chen, Z Wu, C L Masters, C Zhong, N Jing, Y Wang, Y Wang
Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay...
July 11, 2017: Molecular Psychiatry
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