Hallmarks of Alzheimer's disease in stem cell-derived human neurons transplanted into mouse brain
Amaia Arranz Mendiguren
KU Leuven (Belgium)
Our understanding of Alzheimer's disease (AD) pathogenesis is currently limited in part due to the inability to accurately reproduce human pathology. Rodent models of AD have provided important information but do not fully recapitulate crucial aspects of the disease process suggesting that human specific factors might be important in the development of the full pathogenic cascade leading to AD.
In recent studies, the use of human pluripotent stem cells (PSCs) is revealing important mechanisms associated to AD and providing important clues for the identification of candidate drugs. Human PSCs can be differentiated into neurons and allow the investigation of AD-specific phenotypes and mechanisms that cannot be evaluated in other organisms. However, it remains crucial to combine these in vitro approaches with in vivo experiments to study human neurons in the context of the diseased brain.
In this context, we have recently generated a novel chimeric model of AD using the stem cell technology: human PSC were differentiated into neuronal progenitor cells in vitro and then transplanted into the brain of amyloid-β (Aβ) over-expressing mice. During my talk, I will explain how this novel chimeric model of AD recapitulates more accurately the cascade of pathogenic events leading to neurodegeneration, showing that human neurons respond to Aβ pathology differently that the murine neurons in the 3D structure of the brain.