Alzheimer's disease and Frontotemporal Dementia

Neural stem cells derived from patient donor iPSCs and isogenic disease models with neurodegenerative disease-associated mutations
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Alzheimer's disease and frontotemporal dementia

Alzheimer's disease (AD) is a neurodegenerative condition that is strongly linked with age and accounts for 60-70% of all cases of dementia. 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. 


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. 

Cat. No. Product Name Starting Material Quantity Price
ax0111 Human iPSC-Derived Neural Stem Cells - Alzheimer's Disease Patient (APOE4 HOM) Fibroblasts (87 Yr Female) 1.5 million cells & Neural Plating-XF Medium $560
ax0112 Human iPSC-Derived Neural Stem Cells - Alzheimer's Disease Patient (PSEN1 L286V) Fibroblasts (38 Yr Female) 1.5 million cells & Neural Plating-XF Medium $560
ax0113 Human iPSC-Derived Neural Stem Cells - Alzheimer's Disease Patient (PSEN1 M146L) Fibroblasts (53 Yr Male) 1.5 million cells & Neural Plating-XF Medium $560
ax0114 Human iPSC-Derived Neural Stem Cells - Alzheimer's Disease Patient (PSEN1 A246E) Fibroblasts (31 Yr Female) 1.5 million cells & Neural Plating-XF Medium $560
ax0115 Human iPSC-Derived Neural Stem Cells - Alzheimer's Disease Patient (PSEN2 N141I) Fibroblasts (81 Yr Female) 1.5 million cells & Neural Plating-XF Medium $560
ax0018 Human iPSC-Derived Neural Stem Cells (Healthy male donor) Fibroblasts (74 Yr Donor) 1.5 million cells & Neural Plating-XF Medium $560
ax0019 Human iPSC-Derived Neural Stem Cells (Healthy female donor) Fibroblasts (64 Yr Donor) 1.5 million cells & Neural Plating-XF Medium $560

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. 

Cat. No. Product Name Starting Material Associated Disease Price
ax0019 Human iPSC-Derived Neural Stem Cells (Female) Fibroblasts (64 Yr Donor) N/A (isogenic control) $560
ax0320 axolGEM iPSC-Derived Neural Stem Cells MAPT R406W HOM  Fibroblasts (64 Yr Donor) Frontotemporal dementia, parkinsonism & Alzheimer's disease $1280
ax0321 axolGEM iPSC-Derived Neural Stem Cells MAPT R406W HET  Fibroblasts (64 Yr Donor) Frontotemporal dementia, parkinsonism & Alzheimer's disease $1280
ax0322 axolGEM iPSC-Derived Neural Stem Cells MAPT V337M HOM  Fibroblasts (64 Yr Donor) Frontotemporal dementia & parkinsonism $1280
ax0323 axolGEM iPSC-Derived Neural Stem Cells MAPT V337M HET  Fibroblasts (64 Yr Donor) Frontotemporal dementia & parkinsonism $1280
ax0324 axolGEM iPSC-Derived Neural Stem Cells MAPT P301L HOM  Fibroblasts (64 Yr Donor) Frontotemporal dementia & parkinsonism $1280
ax0325 axolGEM iPSC-Derived Neural Stem Cells MAPT P301L HET  Fibroblasts (64 Yr Donor) Frontotemporal dementia & parkinsonism $1280

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. 

Cat. No. Product Name Product Description Quantity Price
ax0101 Neural Stem Cell Media & Reagent Bundle - Expansion and Synchronous Differentiation (System A) Contains all of the neural media and reagents required to expand and synchronously differentiate Axol neural stem cells and maintain the differentiated cortical neurons See Product Page $1920
ax0102 Neural Stem Cell Media & Reagent Bundle - Synchronous Differentiation (System B) Contains all of the neural media and reagents required to synchronously differentiate Axol neural stem cells and maintain the differentiated cortical neurons See Product Page $920
ax0103 Neural Stem Cell Media & Reagent Bundle - Expansion and Spontaneous Differentiation (System C) Contains all of the neural media and reagents required to expand and spontaneously differentiate Axol neural stem cells and maintain the differentiated neural cells See Product Page $1760
ax0104 Neural Stem Cell Media & Reagent Bundle - Spontaneous Differentiation (System D) Contains all of the neural media and reagents required to spontaneously differentiate Axol neural stem cells and maintain the differentiated neural cells See Product Page $760
ax0051 ReadyFect Transfection reagent optimized for transfection of NSCs 40 μL $144

Presentation, posters and citations

Develop an iPSC-derived cell model for Alzheimer’s disease

Dr Alfredo Cabrera, Janssen Pharmaceutica presented relevant model of tau aggregation using iPSC-derived neurons that can provide a better understanding of tau pathophysiology and be useful for identifying novel treatments in Alzheimer's disease.

'Modelling Alzheimer's Disease: A High Throughput-Compatible Assay for Detecting Tau Aggregates Using iPSC-Derived Cortical Neurons in a 3D culture format'

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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

We describe a robust, scalable and disease relevant model of tau aggregation using iPSC- derived cortical neurons that can be applied to drug discovery programs in neurodegeneration.

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

Induced pluripotent stem cell (iPSC)-derived neural cells provide a powerful tool that can be used to model neuronal behaviour and disease pathology. The increased use of these cells in drug discovery promises to help accelerate current drug screening processes and reduce the use of in vivo models used at the earliest stages of testing. Importantly, the production of specific populations, such as cortical and dopaminergic neurons, has allowed researchers to investigate the activity of neural networks from particular regions of the brain. We developed a number of endpoint assays using human iPSC-derived neural stem cells to determine the functionality of these cells and their response to toxins or disease-relevant biomarkers in both Alzheimer’s disease and epilepsy. We have also manipulated the cells using lentivirus and have demonstrated long-term expression of over 9 months. The methods developed offer a platform to facilitate our understanding of normal physiological functions and the causes of central nervous system (CNS) pathology.

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Peer-reviewed publications