3D culture models of Alzheimer's disease: a road map to a "cure in a dish"
Alzheimer's disease (AD) transgenic mice have been used as a standard AD model for basic mechanistic studies and drug discovery. These mouse models showed symbolic AD pathologies including b amyloid (Ab) plaques, gliosis and memory deficits but failed to fully recapitulate AD pathogenic cascades including robust phospho tau (p tau) accumulation, clear neurofibrillary tangles (NFTs) and neurodegeneration, solely driven by familial AD (FAD) mutation(s) Recent advances in human stem cell and three dimensional (3D) culture technologies made it possible to generate novel 3D neural cell culture models that recapitulate AD pathologies including robust Ab deposition and Ab driven NFT like tau pathology. These new 3D human cell culture models of AD hold a promise for a novel platform that can be used for mechanism studies in human brain like environment and high throughput drug screening (HTS) In this review, we will summarize the current progress in recapitulating AD pathogenic cascades in human neural cell culture models using AD patient derived induced pluripotent stem cells (iPSCs) or genetically modified human stem cell lines. We will also explain how new 3D culture technologies were applied to accelerate Ab and p tau pathologies in human neural cell cultures, as compared the standard two dimensional (2D) culture conditions. Finally, we will discuss a potential impact of the human 3D human neural cell culture models on the AD drug development process. These revolutionary 3D culture models of AD will contribute to accelerate the discovery of novel AD drugs.
Molecular Neurodegeneration