Alzheimer's Disease Models Service

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

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.

3D Cellular Models in AD

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.

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.

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.

Reference

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.

For Research Use Only. Not For Clinical Use.

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