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Alzheimer's Disease Models Service
Introduction to Alzheimer's Disease Models
Overview of Alzheimer's Disease
Alzheimer's disease (AD) presently occupies the topmost position among the most diagnosed neurodegenerative diseases worldwide, with the number of affected people forecasted to reach 100 million by 2050. According to the latest statistics, nearly 44 million people in the world suffer from AD or related dementia, with only one in four being diagnosed with the disease. Currently, the disease has no cure available for its treatment, except for some relief from some of the symptoms. Besides its multifactorial and heterogeneous nature, AD is also progressive, i.e., the symptoms gradually worsen with the passage of years. Multiple risk factors including genetic and environmental sources have been implicated in the emergence of AD, with advancing age being identified as the most significant among them.
In Vitro Models in AD
- Cellular Models in AD
- 3D Cellular Models in AD
An effective AD cellular model utilizes the appropriate cell type, corresponding to the specific AD-affected brain region, and then recapitulates all relevant pathological features in a reproducible manner, over a reasonably practical duration of culture. In vitro models of AD are usually created either by introducing synthetic compounds like the Aβ peptide into the cells or by inserting AD-associated genes into cells via gene delivery technologies such as transfection and transduction. The models developed using the former technique are limited by the fact they do not display progressive pathogenesis as seen in the AD human brain, and hence latter models which utilize mutated genes are more popular at present.
The various advantages offered by 3D over 2D cellular cultures have been well acknowledged, especially in the provision of cues influencing cell structure, adhesion, proliferation, signaling, and mechanotransduction. This is also relevant in neuronal cultures, where a 3D substrate helps improve both cell yield and cell differentiation in comparison to traditional 2D dishes. 3D cell cultures allow cell-to-cell interaction, especially between neurons and glia, and therefore are more representative of the complex interdependent nature of the microenvironment present inside the brain. Moreover, cells in 3D mimic the native target tissues in drug testing more accurately and allow the assessment of the effect of drugs in terms of the spatial features of the microenvironment native tissue via microscopy. The spatial configuration of neurons may also affect the cytoskeletal dynamics such as the binding of tau to microtubules and therefore, more accurately represented using 3D culture platforms.
| 3D Approach Utilized | Methodology/Cell Culture Type | Initial Cell Type | Differentiated Cell Type | Duration of Culture and key Focus |
|---|---|---|---|---|
| Aggregate based | Organotypic-like spheroid culture | SH-SY5Y (3 lines) | - | 5-7 days, Tau pathology |
| Aggregate based | Networked neurosphere culture | Prenatal rat cortical neurons (NPC) | Neurons | 10 days, Aβ pathology |
| Scaffold based | Matrigel matrix based thin and thick layer culture | ReNcell VM (ReN) human neural precursor (hNPC) cells | Neurons and glia | 10-14 weeks, Aβ and Tau pathology |
| Microfluidics + Aggregate based | Brain-on-a-chip neurospheroidal culture | Prenatal rat cortical neurons (NPC) | Neurons | 10 days, Aβ pathology |
| Scaffold based | Self-assembling peptide hydrogel matrix-based culture | Healthy human iPSC derived neuroepithelial stem cells (It- NES) | Neurons | 2 days, P21- activated kinase modulation |
| Aggregate based | Cortical neurospheroidal culture | SAD Human iPSC derived from blood cells | Neurons | 9 weeks, Aβ and Tau pathology |
| Aggregate based | Neural organoid culture | FAD Human iPSC derived from fibroblasts | NPC and neurons | 90 days, Aβ and Tau pathology |
| Scaffold based | Matrigel matrix based thin layer culture | Healthy human iPSC derived from epithelial cells, fibroblasts | Layer V cortical neurons | 40 days, Tau pathology |
| Scaffold based | Collagen matrix- based culture | PC-12 cells, SH-SY5Y cells | - | 4-6 days, Aβ pathology |
| Aggregate + Scaffold based | Neurospheroids suspended in Matrigel matrix | ReNcell VM human neural stem (ReN) cells and human iPSC- derived neural progenitor cells (hiPSC) | Neurons and glia | 8 weeks, Aβ and Tau pathology |
Table 1: 3D in vitro Models of AD.
Services at Creative Biolabs
Creative Biolabs is an experienced custom in vitro CNS disease modeling services provider. We have been focusing on this field for more than 10 years and have developed a comprehensive technology platform. Our platform is now mature in offering various in vitro CNS disease services, including Alzheimer's disease models. With strong foundations, rich experience, and extensive expertise, we are confident in the quality of our services.
If you are interested in ex vivo Alzheimer's disease models, or any other custom CNS diseases modeling services, please don't hesitate to contact us for more information.
- Genetically Engineered Models: Our service includes the development of genetically engineered animal models, primarily mice and rats, to mimic Alzheimer's disease. These models are developed by introducing specific mutations associated with familial Alzheimer's disease, such as mutations in the APP, PSEN1, and PSEN2 genes, into animal genomes.
- Cell Cultures: We provide an array of cell culture models including immortalized cell lines, primary cultures, and human iPSC-derived neural cells. By manipulating specific genes and/or exposing these cell cultures to various biochemical factors, the neurons show characteristics of early and advanced stages of Alzheimer's disease.
- In vitro 3D Brain Organoid Models: Our service includes the generation of complex 3D organoid models of the human brain derived from patient-specific iPSCs. These are especially valuable in Alzheimer's research, as they can recreate disease pathogenesis in a controlled setting.
We ensure comprehensive phenotypic characterization and pathology evaluation. This includes assessments of cognitive decline and behavioral changes, amyloid beta plaque buildup, tauopathy, neuroinflammation and neurodegeneration, to name a few. Our company also offers custom model development services that can be tailored to the specific needs of our clients' research goals.
We also offer other related services, including but not limited to:
| Services | Descriptions |
|---|---|
| Custom Neural Differentiation | As experienced experts in neuroscience modeling, we offer comprehensive customized neural differentiation services to effectively support your neuroscience research. |
| High-throughput Phenotypic Screen | Mitochondrial dysfunction is a common mechanism and phenotype shared by many neurological disorders. We can provide phenotypic screening services for application in new drug discovery. |
| Primary Cell Lines | We offer the development of neuroscience-based primary cell lines and related customized products. |
Published Data
DANA M. CAIRNS, et al. reported a herpes-induced AD tissue model that mimics the human disease with multicellular amyloid plaque-like formations, neurogliosis, neuroinflammation, and functional decline in the complete absence of any exogenous AD mediators.
They used human induced neural stem cells (hiNSC) and HSV-1 infection to generate physiologically relevant human tissues in a 3D bioengineered brain model to study AD. Immunostaining was used to identify whether the phenotypic features of AD were induced in HSV-1-infected hiNSC. As shown, the results showed that HSV-1 caused reactive gliosis and inflammation reminiscent of neurodegeneration in hiNSC.
Fig. 2 HSV-1 causes reactive gliosis and inflammation reminiscent of neurodegeneration in hiNSCs.2
Application of In Vitro Models in AD Research
Yagi et al. were the first to generate iPSCs from AD patients, harboring mutations in PSEN1 (A246E) and PSEN2 (N141I) and demonstrated increased Aβ42 secretion along with an elevated Aβ42 to Aβ40 ratio in the iPSC derived neurons as compared to those from non-AD controls. They also studied the response of the secreted Aβ42 levels to a known γ-secretase inhibitor with positive results indicating the potential of candidate drugs for AD treatment.
Another study by Kondo et al. showed intracellular accumulation of Aβ oligomers in both FAD (APP-E693D mutation) and SAD cases, inducing both endoplasmic reticulum (ER) and oxidative stress in the iPSC derived neurons. The accumulated Aβ oligomers were not proteolytically resistant and treatment of the AD neural cells with docosahexaenoic acid (DHA) resulted in alleviation of stress responses, paving the way for the development of anti-AD drugs.
FAQs
Q: What part of Alzheimer's pathology does your disease model focus on?
A: The models developed focus on key pathological features such as beta-amyloid plaque accumulation, neurofibrillary tangles, and neurodegeneration. However, the focus can be tailored depending on your specific research interests. We understand that every researcher's needs are unique. Our expert team will discuss your specific research objectives and accordingly suggest the most fitting model development strategy.
Q: What are the costs associated with developing an Alzheimer's disease model?
A: The costs of developing an Alzheimer's disease model depend on several factors, including the type of model, the extent of customization, and the specific requirements of the project. We offer a detailed cost estimate after an initial consultation, taking into account all aspects of model development. We aim to provide competitive pricing and offer various packages to fit different budgetary needs.
Q: What kind of data and documentation will I receive with the developed model?
A: With each developed Alzheimer's disease model, we provide comprehensive data and documentation, including genotyping reports, phenotypic characterization, functional assay results, and detailed protocols for model maintenance and experimentation. This documentation ensures that researchers have all the necessary information to effectively use and validate the models in their studies.
Q: What kind of support do you provide during the model development process?
A: We provide comprehensive support throughout the model development process, including initial consultation, regular updates, and troubleshooting assistance. Our team of experts is available to discuss project requirements, provide technical guidance, and address any challenges that arise. We also offer training sessions and detailed protocols to help researchers effectively use and manage the developed models.
Scientific Resources
References
- Ranjan, V. D., et al. Modelling Alzheimer's disease: Insights from in vivo to in vitro three-dimensional culture platforms. J Tissue Eng Regen Med. 2018, 12(9): 1944-1958.
- Cairns, Dana M., et al. "A 3D human brain–like tissue model of herpes-induced Alzheimer's disease." Science advances 6.19 (2020): eaay8828.
For Research Use Only. Not For Clinical Use.