Alzheimer's disease and Frontotemporal Dementia

Human iPSC-derived neural stem cells from Alzheimer's disease patients

Fibroblasts from patients, clinically diagnosed with Alzheimer's disease, were reprogrammed to iPSCs using our footprint-free episomal reprogramming method and then differentiated to neural stem cells using our chemically defined cortical neural induction method. Neural stem cells are available from Alzheimer's patients with mutations in the presenilin-1 (PSEN1) and presenilin-2 (PSEN2) genes as well as a patient homozygous for the APOE4 allele. Neural stem cells from healthy donor iPSCs are also available as suitable controls.

Isogenic human iPSC-derived neural stem cells

Using CRISPR-Cas9 gene editing technology, disease-associated mutations were introduced into iPSCs that were then differentiated to neural stem cells using our fully defined cortical neural induction method. Isogenic control neural stem cells are also available, permitting highly targeted experiments and screening studies into the effects of pathogenic tau associated with frontotemporal dementia and Alzheimer's disease. The mutations introduced into the MAPT(tau) gene alter the amino acid sequence of the protein (R406W, V337M, P301L), which can accelerate tau aggregation or affect the phosphorylation or binding affinity of tau. Axol isogenic Alzheimer's disease models and isogenic frontotemporal dementia disease models were co-developed with Horizon Discovery, combining Horizon's expertise in gene editing with Axol's expertise in iPSC reprogramming and neural stem cell differentiation.

Neural cell culture media and reagents

Cell culture media and reagents developed by Axol scientists for optimal plating, expansion, differentiation and maintenance of neural stem cells and cerebral cortical neurons in a wide range of culture formats and applications. The cell culture reagents are grouped into simple bundles for increased convenience and value.

• Next-generation neurological disease models: isogenic tools for investigating frontotemporal dementia, Alzheimer's and Parkinson's diseases

• Functional phenotypic characterization of iPSC-neurons from Alzheimer’s disease patients carrying PS-1 mutation in drug screening and disease modeling

• Characterization and potential applications of human iPSC-derived neural stem cells

• Modelling neurological disease: in vitro gene editing and iPSC differentiation combine to create powerful new tools

• Induction of plasticity phenomena in human induced pluripotent stem cell-derived cortical neurons

• Functional maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture

• Pharmacological responses in cultured human iPSC-derived cortical neurons using multi-electrode array

• In vitro electrophysiological drug testing using human induced-pluripotent stem cells

• Implementation of high throughput screening on iPS cells

• Using iPSC-derived neural stem cells as a CNS model to study neuronal behaviour in development and neurodegernation

• Modelling Alzheimer's disease: Development of a scalable, high-throughput-compatible assay to detect tau aggregates using iPSC-derived cortical neurons maintained in a 3D-culture format

• Lin L, Juan Y, Bjoern S, et al., In vitro differentiation of human neural progenitor cells into striatal GABAergic neurons. Stem Cells Translational Medicine (2015)

• Verheyen A, Diels A, Dijkmans J, et al., Using human iPSC-derived neurons to model TAU aggregation. PLoS One (2015)

• Odawara A, Katoh H, Matsuda N, et al., Induction of long-term potentiation and depression phenomena in human induced pluripotent stem cell-derived cortical neurons. Biochemical and Biophysical Research Communications (2015)

• Cacabelos D, Ayala V, Granado-Serrano AB, et al., Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis. Neurobiology of Disease (2016)

• Medda X, Mertens L, Versweyveld S, et al., Development of a scalable, high-throughput-compatible assay to detect TAU aggregates using iPSC-derived cortical neurons maintained in a three-dimensional culture format. Journal of Biomolecular Screening (2016)

• Odawara A, Katoh H, Matsuda N, et al., Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture. Scientific Reports (2016)

• Wang W, Wang L, Lu, J, et al., The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Nature Medicine (2016)

• Szabo A, Kovacs A, Riba J, et al., The endogenous hallucinogen and trace amine N,N-dimethyltryptamine (DMT) displays potent protective effects against hypoxia via sigma-1 receptor activation in human primary iPSC-derived cortical neurons and microglia-like immune cells. Frontiers in Neuroscience (2016)

• Wevers NR, van Vught R, Wilschut KJ, et al., High-throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform. Scientific Reports (2016)

• O'Rourke C, Lee-Reeves C, Drake RAL, et al., Adapting tissue-engineered in vitro CNS models for high-throughput study of neurodegeneration. Journal of Tissue Engineering (2017)

• Poulsen ET, Iannuzzi F, Rasmussen HF, et al., An aberrant phosphorylation of amyloid precursor protein tyrosine regulates its trafficking and the binding to the clathrin endocytic complex in neural stem cells of Alzheimer's disease patients. Journal of Frontiers in Molecular Neuroscience (2017)

• Jones VC, Atkinson-Dell R, Verkhratsky A et al., Aberrant iPSC-derived human astrocytes in Alzheimer's disease. Cell Death and Disease (2017)

• Gunhanlar N, Shpak G, van der Kroeg M et al., A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Molecular Psychiatry (2017)

• Zollo A, Allen Z, Rasmussen H et al., Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer’s Disease Patients Carrying the APOE Epsilon 4 Allele. Neural Plasticity (2017)

• Cho S.J, Park M.H, Han C et al., VEGFR2 alteration in Alzheimer’s disease. Scientific Reports - Nature (2017)

• Rao A.N, Patil A, Brodnik Z.D et al., Pharmacologically increasing microtubule acetylation corrects stress-exacerbated effects of organophosphates on neurons. Traffic - Wiley Online Library (2017)

• Synder C, Yu L, Ngo T et al., In vitro assessment of chemotherapy-induced neuronal toxicity Science Direct (2017)

• Matsuda N, Odawara A, Katoh H et al., Detection of synchronized burst firing in cultured human induced pluripotent stem cell-derived neurons using a 4-step method Science Direct (2018)

• Basuodan R, Basu A.P, Clowry G.J et al., Human neural stem cells dispersed in artificial ECM form cerebral organoids when grafted in vivo Journal of Anatomy - Wiley Online Library (2018)

• Nizou G, Wicks R.T, Wicks E.E et al., Human cortex spheroid with a functional blood brain barrier for high-throughput neurotoxicity screening and disease modeling Nature (2018)

• van Pel D.M, Harada K, Song D et al., Modelling glioma invasion using 3D bioprinting and scaffold-free 3D culture Journal of Cell Communication and Signaling (2018)

• Kahn O.I, Schätzle P, van de Willige D et al., APC2 controls dendrite development by promoting microtubule dynamics Nature (2018)

• Relevance of iPS cells in cell based screening and drug development

• Frontotemporal dementia and Parkinson's Disease cellular models: In vitro characterization of pathological phenotypes in gene-edited iPSC-derived neurons with MAPT and LRRK2 mutations

• Abnormal phosphorylation of amyloid precursor protein tyrosine residues alters the APP trafficking in neurons from Alzheimer's Disease affected patients

• Modeling FTDP-17 linked tauopathies and Alzheimer's disease with human iPSC

• Electrophysiological maturation and pharmacological responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture

• The use of iPSC-derived cells and primary cells as in vitro models for toxicity screening

• Modeling Alzheimer's disease using stem cells

• Rising to the challenges of human iPSC-derived cells for tox & drug screening

• Induced Pluripotent Stem Cells: recapitulating disease to facilitate drug discovery

• Using human iPSC-derived cortical neurons for the early prediction of neurotoxicity

• Are 3D neural cell cultures the best translational models towards finding a cure for Alzheimer's disease?

• Using neural stem cells for safety pharmacology studies

• A suffering relationship in Alzheimer's disease

• iPSC-Derived Neurons for Epilepsy Studies

• Nurturing Neuroscience