AD In Vitro Disease Models
Alzheimer's disease (AD) is one of the most concerning neurodegenerative diseases. As a global leading CRO company focusing on neuroscience research, Creative Biolabs has an advanced technology platform providing various kinds of AD in vitro model services to help accelerate AD studies.
Overview of AD
AD, also known as the most common form of dementia, is a progressive, neurodegenerative disorder in adults, afflicting 35.6 million individuals worldwide. Although a variety of therapies have been developed over the years to treat patients with AD, none of these treatments are able to provide a cure, but merely alleviate the AD-associated symptoms. After recognizing the contributing role of synaptic loss in memory deficits, researchers have attributed the poor therapeutic effects in patients with AD to the pathological features of this disease.
Fig.1 Schematic diagram of the pathogenesis of AD. (Li, 2016)
AD In Vitro Models
In order to explore more effective treatments, a more complete understanding of the pathophysiology of AD is required. Animal models can reproduce the overt changes occurring in patients with AD. However, complex in vivo conditions may limit the accessibility to the tissue of interest and prevent real-time and spatial measurements of biological changes. Consequently, several in vitro experimental models of AD, which provide detailed regional and cell-level information, have been developed to enhance the usefulness of in vivo animal models. All these models are of value for deciphering the fundamental mechanisms underlying AD pathology and also, for the testing of novel therapies targeted against this disease.
- Tissue models.
Brain tissue, cultured in vitro, provides a good platform for studying the impact of AD-associated substances, such as Aβ on nerve cells. Due to the ease of manipulation and the controllable environments, these models are also used to test therapeutics targeted at AD pathophysiology and to reveal the underlying molecular mechanisms.
- Cell models.
Progress in stem cell techniques has broadened our horizons for in vitro disease modeling. For AD, disease-specific induced pluripotent stem cell (iPSC) lines have been generated from patients with sAD or fAD, providing an effective approach for disease modeling and drug discovery. As iPSC lines from patients with sAD carry different genetic variants, the generation of sufficient stem cells is required to fully guide drug development and enhance our understanding of AD.
- Molecular simulation models.
In previous studies, researchers have created an NADPH oxidase-nitric oxide system as anti-bubble bio machinery, to imitate the inflammatory cascade seen in AD. This bio machinery induced neuronal death by triggering a guanylyl-cyclase-mediated inflammatory cascade. Researchers have also reported the establishment of molecular dynamics simulations of model systems that are comprised of an Aβ40 peptide in water in interaction with β-sheet breakers mimicking the 17-21 region of the Aβ40 sequence, showing that β-sheet breakers inhibit Aβ40 aggregation by stabilizing its native structure. These studies have provided us with streamlined approaches to dissecting the molecular functions of endogenous regulatory pathways involved in AD, permitting the direct mechanistic studies of the modulators of these pathways. These approaches are also used to screen possible therapeutic compounds efficiently and evidently.
| Models | Identified aspects of AD | Advantages | Limitations |
|---|---|---|---|
| Tissue models | |||
| Cultured tissues |
Biochemical changes; p-Tau; amyloidosis; neuron degeneration |
Show the AD mechanism at molecular and cellular level; controllable environment |
No neurological changes; no plaques; no NFTs |
| Brain slices |
Biochemical changes; p-Tau; amyloidosis; neuron degeneration |
Show pathology biochemically and histologically; natural physiological environment | Refer to the above |
| Cell models | |||
| iPSC |
Biochemical changes; p-Tau; amyloidosis; neuron degeneration |
Similar genetic background to humans | No pathological and neurological changes |
| Neuroblastoma cell | Specific molecular pathway like APP processing | Rapid and direct | No pathological and neurological changes |
| Molecular simulation model | |||
| Antibubble bio machinery | Inflammatory reactivation; neuronal death | Dissect molecular functions of endogenous regulatory pathways in AD | No pathological and neurological changes |
In vitro models play important roles in AD mechanism research and therapeutic research. Creative Biolabs has years of experience focusing on neuroscience research and provides quality-assured AD in vitro model services. Our services cover tissue-based models, cell-based models, molecular-based models, etc. With advanced technology platforms and professional experts, we are confident in offering customer-satisfied services.
If you are focusing on neuroscience research and AD studies, or you have any other questions about our services, please feel free to contact us for more information.
Reference
- Li, X.; et al. Experimental models of Alzheimer's disease for deciphering the pathogenesis and therapeutic screening (Review). Int J Mol Med. 2016, 37(2): 271-83.
