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Animal Model Induction - Alzheimer's Disease
Alzheimer's disease (AD) is a progressive neurodegenerative disease that slowly destroys neurons and leads to severe cognitive impairment. To date, there is still no cure and the main focus is on improving symptoms, making it difficult to reverse the disease process. Animal models are essential for studying the pathogenesis of neurodegenerative diseases and developing their therapeutic approaches. Good animal models can better simulate the disease state and help researchers explore the disease etiology and pathogenesis of AD.
Creative Biolabs shares several methods of constructing animal models of AD and their advantages and disadvantages. We offer AD model services and other modeling services. Please click for specific information.
| Services | What We Do | Advantages |
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| Alzheimer's Disease Models | Creative Biolabs is an experienced provider of custom in vitro CNS disease modeling services. We specialize in this field and have developed a comprehensive technology platform. Our platform can provide a variety of in vitro CNS disease services, including Alzheimer's disease modeling. |
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| Parkinson's Disease Models | We are now able to offer a wide range of customized services for modeling ex vivo CNS diseases, including Parkinson's disease models. A large amount of research data on the pathophysiologic mechanisms of Parkinson's disease can be obtained using our in vitro experimental models. |
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| Huntington's Disease Models | We can develop stem cell-based ex vitro HD models to analyze their pathophysiology or drug screening, including mimicking abnormal mitochondrial function. |
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Alzheimer's Disease Modeling - Animal Selection
The following animal types are commonly used in AD disease modeling.
- Rodent Models - Rodents have relatively short lifespans, are more likely to reproduce rapidly, are cheaper, have available gene editing technology, and have well-established behavioral testing methods. However, most rodent models fail to reproduce the obvious and typical neurodegeneration of patients.
- Zebrafish Models - Zebrafish possess vertebrate neurostructural organization, with all major structures similar to the mammalian brain, and have a functional blood brain barrier similar to that of humans. With its short life cycle and high fecundity, zebrafish is particularly suitable for large-scale drug screening.
- Non-human Primate Models - Brain development, anatomy, and cognitive and behavioral complexity are closer to those of humans; brains are much larger than those of small animals and have folded cortical surfaces; there is greater genetic similarity to humans; pathological development is more similar; and there is usability for disease assessment, but the animals have long reproduction cycles, are expensive, and are not well developed for genetic modification.
Comparison of Classical AD Animal Models
We provide specific information on several classical AD animal models.
| Model Types | Descriptions | Examples |
|---|---|---|
| Transgenic models | AD transgenic models are the most commonly used models for the study of AD. AD transgenic models mainly include APP transgenic model, Tau protein transgenic model PSEN1 transgenic model, APOE transgenic model, double transgenic model, and multi-transgenic model. |
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| Non-transgenic models | Natural aging AD model: No intervening factors are needed, it can develop spontaneously, and the aging symptoms of the model animals are similar to those of AD patients. However, these animals do not spontaneously develop pathologic features typical of AD (e.g., amyloid deposition). | Natural aging AD models can be used to conduct studies related to the relationship between physiologic aging and AD. |
| Induced AD model: AD characteristics can be mimicked by administering drugs to the animal. Different modeling methods differ in terms of the drug administered, the dosage, the mode of administration, the route of administration, the site of administration, and the pathologic characteristics of the modeled animal. |
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Modeling Methods for Induced AD Models
Hyperphosphorylation of the microtubule-associated protein tau at specific sites is a well-recognized pathological process in AD, and PKA is a key kinase in the hyperphosphorylation of AD-like tau. In addition to the above features, patients with AD also have pathological features such as oxidative stress, neuroinflammation, mitochondrial dysfunction, microglial activation, cell-cycle dysregulation, and cholinergic dysfunction, which allow them to build up a model of AD.
- Wortmannin induces hyperphosphorylation of Alzheimer-like tau.
Wortmannin is a potent, irreversible and selective PI3K inhibitor. Wortmannin was injected into the lateral ventricle of rats using the Stereotaxic technique. Wortmannin activates GSK-3 by inhibiting PI3K through the down-regulation of PKB, which in turn reduces the phosphorylation of GSK-3, which phosphorylates modified Tau proteins and causes aberrant phosphorylation of Tau. The tau hyperphosphorylation induced by Wortmannin was detected mainly in the hippocampal pyramidal neurons, and swelling was also seen in the same region of the brain. Wortmannin-induced tau hyperphosphorylation was detected mainly in hippocampal pyramidal neurons, and swollen axons and detached myelin sheaths were also seen in the same region of the brain.
- Isoprenaline induces hyperphosphorylation of Alzheimer-like tau.
Isoprenaline is a specific activator of cAMP-dependent kinase (PKA). Isoprenaline injected bilaterally into the rat hippocampus hyperactivated PKA, calcium/calmodulin-dependent kinase II and cyclin-dependent kinase-5, inhibited protein phosphatase-2A, and induced tau hyperphosphorylation at the PHF-1 and tau-1 sites, increased oxidative stress to further induce aberrant tau hyperphosphorylation, and interfered with spatial memory retention 48 hours after drug injection.
- Haloperidol induces tau hyperphosphorylation.
Haloperidol is a typical antipsychotic compound that triggers oxidative stress and neuronal damage during treatment, leading to cytoskeletal collapse and hyperphosphorylation of tau proteins.
- Colchicines induce sporadic AD in animal models.
Colchicines selectively destroy the granule cell nucleus vertebral cells in the hippocampus, induce neurogenic fiber deformation, choline acetyltransferase decline, neuronal apoptosis, etc., and at the same time, significantly induce elevated levels of oxidative stress, which collectively led to cognitive dysfunction in rats, whose learning and memory abilities were significantly reduced.
- Scopolamine induces cholinergic dysfunction in aged animals.
Cholinergic dysfunction is thought to play an important role in aging and memory loss in Alzheimer's disease. Scopolamine is a nonselective muscarinic cholinergic antagonist. The Scopolamine-induced cholinergic dysfunction model in aged animals can be used to examine early pathological events in the development of AD.
As a leading service provider of CNS disease modeling, we have the information to provide a good animal model that can help researchers explore AD.
For Research Use Only. Not For Clinical Use.