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SETTING UP THE MODEL OF ALZHEIMER’S DISEASE USING STEM CELLS-DERIVED CEREBRAL ORGANOIDS
Abstract
Aims
The advancements in stem cell technology and the possibility of obtaining stem cells directly from patients represent a great promise of modeling complex neurodegenerative diseases, including Alzheimer’s disease, in vitro. Thus, our study aimed to create an in vitro model of Alzheimer’s disease (AD) directly from patients’ cells and subsequently to study the development of AD pathogenesis.
Methods
Using cell reprogramming, we successfully created induced pluripotent stem cells from cells of three patients with familial AD as well as from three healthy controls. We subsequently created 3D cerebral organoids (miniature organs resembling the human brain). We tested the presence of AD-specific pathology (i.e., accumulation of Aβ and p-Tau) using numerous methods including ELISA, qPCR, Western blot, and targeted MS.
Results
Our results show that AD-iPSC-derived cerebral organoids mimic the development of AD pathology in vitro. They also show the signs of synaptic loss, cellular stress, and senescence. Additionally, by collecting several consecutive time points of the cerebral organoid development, we were able to map the development of these pathologies in vitro. Lastly, using this cell system, we are currently testing several hypotheses on the primary cause of Aβ accumulation.
Conclusions
Altogether, our data will not only help to elucidate the development of AD pathology but will also allow the testing of substances that may prevent its development under in vitro conditions.