Experimental models of Alzheimer's disease
[2][4] Researchers commonly use post-mortem human tissue or experimental models to conduct experiments relating to Alzheimer's disease.
These models often have genetic modifications that enable them to be more representative of human Alzheimer's disease and its associated pathology: extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs).
Traditional two dimensional cell culture is a useful experimental model of Alzheimer's disease to conduct experiments in a high throughput manner.
[7] This method requires dissection of the desired brain region from rodent tissue followed by digestion, dissociation, and plating steps.
[10] When initially cultured, these cells are spherical and over time begin to form axons, dendrites, and eventually develop synaptic connections.
[11] iPSCs have also been shown to exhibit genomic instability and develop additional mutations when passaged (harvested and reseeded into daughter cultures) numerous times, posing both safety concerns for patient use as well as potential reproducibility problems in experimental studies.
[5][24] Common issues arising from the use of 3D cultures is the lack of vasculature within the organoid, leading to cell death and dysfunction at inner layers.
efforts are focusing on introducing endothelial cells into guided formation cultures in order to create vascular systems and provide nutrient distribution to deep layers.
investigating common transcriptional profiles associated with Alzheimer's disease and aging in order to reintroduce these landscapes into iPSCs for future biomedical research and therapeutic development.
[9][25] These systems additionally introduce physiological cues such as fluid sheer stress, tension, and compression which allows these in vitro conditions to better resemble the in vivo environment.
[10] These systems can also be developed incorporating brain endothelial cells to mimic the blood–brain barrier, making this an extremely useful model for BBB dysfunction in Alzheimer's disease, screening novel therapeutics potential to pass from the blood into the brain, therapeutic pharmacokinetics, as well as drug adsorption, distribution, metabolism, elimination, and toxicity (ADMET) tendencies.
[26] Mice and rats on average tend to live for 2 years, a much shorter lifespan than humans, presenting both limitations as well as benefits for more rapid experiment completion.
[5] In order to recapitulate and accelerate human Alzheimer's disease pathology, scientists commonly introduce FAD associated mutations.
[6] This results in the animal models having a higher tendency to form amyloid-β plaques and/or neurofibrillary tangles, the two pathological hallmarks of Alzheimer's disease.
These rodent models are often used to test and develop drugs treating Alzheimer's disease before progressing to clinical trials in humans.
