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Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative condition that is strongly linked with age and accounts for 60-70% of all cases of dementia.
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Early onset Alzheimer’s disease, which accounts for approximately 2-3% of AD cases, is a hereditary condition that is strongly associated with mutations in presenilin-1 (PSEN1), amyloid precursor protein (APP) and presenilin-2 (PSEN2) genes. Late onset Alzheimer’s disease occurs after the age of 65 and accounts for the vast majority of cases.

A combination of factors increase the risk of developing Alzheimer’s disease. One of the strongest risk factors is having two copies of the APOE4 allele, which increases the risk of developing late onset Alzheimer’s disease by approximately 15 times.

Frontotemporal dementia (FTD) refers to a spectrum of clinical diseases that may have several different underlying pathologies. Frontotemporal dementia can be sporadic or associated with mutations in the MAPT (microtubule-associated protein tau) and progranulin genes, and C9ORF72 repeat expansions.

These genetic mutations can lead to accumulation of TDP43 protein or tangles of MAPT (tau) protein. Currently, there are no approved treatments or reliable biomarkers for frontotemporal dementia. There is a need for in vitro human cell models for frontotemporal dementia and Alzheimer’s disease that can be used to accelerate research and assist in the development of new drugs to treat these disorders.

Alzheimer's Disease

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.

Product ax0019 is the healthy isogenic control for the following cell lines:

Resources

Protocols

Enriched Cerebral Cortical Neuron Protocol
Spontaneous Neuronal Differentiation Protocol
Data – APOE Genotyping of Axol NSCs and Astrocytes

Posters

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

Product citations

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)

Presentations

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
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