3D-bioprinted model of adult neural stem cell microenvironment in Alzheimer’s disease

Neurogenesis plays a major role in neuroplasticity and memory. In adult human and mouse brains, neural stem cells (NSCs) are mainly distributed in two extensively characterized neurogenic niches: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. Impaired neurogenesis is one of the consequences of Alzheimer’s disease (AD), contributing to cognitive decline and progressive memory loss. Developing new in vitro models that resemble this three-dimensional (3D) structure is fundamental for enhancing our understanding of the SVZ neurogenic niche dynamics in AD. Herein, we produced and characterized a 3D-bioprinted model of the adult SVZ neurogenic niche containing amyloid β (Aβ) oligomers, mimicking the NSC microenvironment in AD. In this model, Aβ oligomers induce oxidative stress and reduce the proliferative potential of NSCs, while stimulating neuronal differentiation. We hypothesize that these events are an early attempt of adult NSCs to compensate for neuronal death in AD pathogenesis. Our 3D model simulates the NSC niche physiology, reproducing an early response of NSCs in AD, strengthening the importance of studying the potential of neurogenesis in neurodegeneration.