Young Hye Kim

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 β-amyloid (Aβ) 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 Aβ deposition and Aβ-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 Aβ 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.

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The "β-amyloid cascade hypothesis" of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery.

The purpose of the present study was to explore the experiences of aging in adults aged from 40 to 80 years, living in Seoul, Korea, and how these experiences differ according to age. The phenomenological analysis method was used to identify major categories of experience. Five common categories were identified: bodily change; downward spiral of the perspective about aging; acceptance of limitation and boundaries with aging; feelings of nostalgia and hope and; sustaining life through harmony. Results showed that as South Korean adults grew older they began to recognize changes in their bodies. In their 60s, functional changes were explicit and individuals finally admitted that they were getting older. Disease was a part of life, which was inseparable from their daily lives, and death was accepted as a natural event. As South Korean adults grew older, they felt a strong responsibility for their children and tried to live an honest and respectable life. This was a common perception held regarding aging. Thus they pursued a traditional family-oriented life. Even though aging was something that many wished to avoid, it was accepted as part of life. As they experienced the agony of life, they began to accept the realities of living, and wished for their family's happiness and a better future. The present study aimed to increase understanding of the aging experience and to provide a foundation for future research to develop effective health promotion interventions for this population.