Recapitulating amyloid β and tau pathology in human neural cell culture models: clinical implications

Abstract

The "amyloid β hypothesis" of Alzheimer's disease (AD) has been the reigning hypothesis explaining pathogenic mechanisms of AD over the last two decades. However, this hypothesis has not been fully validated in animal models, and several major unresolved issues remain. We recently developed a human neural cell culture model of AD based on a three-dimensional (3D) cell culture system. This unique, cellular model recapitulates key events of the AD pathogenic cascade, including β-amyloid plaques and neurofibrillary tangles. Our 3D human neural cell culture model system provides a premise for a new generation of cellular AD models that can serve as a novel platform for studying pathogenic mechanisms and for high-throughput drug screening in a human brain-like environment.

Keywords: 3D culture model; APP; Alzheimer’s disease; Aβ; Induced pluripotent stem cells; amyloid β; human neural progenitor cells; iPSCs; β-amyloid precursor protein.

Figure 1

Platform for AD drug screening in human neural progenitor cells with FAD mutations in a 3D culture system, which successfully reproduce human AD pathogenesis (amyloid plaques-driven tauopathy).