Disease modeling of Alzheimer's disease (AD) has been hampered by the lack of suitable cellular models while animal models are mainly based on the overexpression of AD-related genes which often results in an overemphasis of certain pathways and is also confounded by aging. In this study, we therefore developed and used induced pluripotent stem cell (iPSC) lines from a middle-aged AD patient with a known presenilin 1 (PSEN1) mutation (Glu120Lys; PS1-E120K) and as a control, an elderly normal subject. Using this approach, we demonstrated that the extracellular accumulation of Aβ was dramatically increased in PS1-E120K iPSC-derived neurons compared with the control iPSC line. PS1-E120K iPSC-derived neurons also exhibited high levels of phosphorylated tau, as well as mitochondrial abnormalities and defective autophagy. Given that the effect of aging is lost with iPSC generation, these abnormal cellular features are therefore indicative of PSEN1-associated AD pathogenesis rather than primary changes associated with aging. Taken together, this iPSC-based approach of AD modeling can now be used to better understand AD pathogenesis as well as a tool for drug discovery.
Aged ; Aging ; Alzheimer Disease* ; Autophagy ; Cerebellar Ataxia* ; Drug Discovery ; Humans ; Models, Animal ; Neurons ; Pluripotent Stem Cells ; Presenilin-1 ; Stem Cells

Shift workers experience a disruption in the circadian sleep-wake rhythm, which brings upon adverse health effects such as fatigue, insomnia and decreased sleep quality. Moreover, shift work has deleterious effects on both work productivity and safety. In this review, we present a brief overview of the current literature on the consequences of shift work, especially focusing on attention-associated cognitive decline and related behavioral changes. We searched two electronic databases, PubMed and RISS, using key search terms related to cognitive domains, deleterious effects, and shift work. Twenty studies were eligible for the final review. The consequences of shift work can be classified into the following three categories extracted from the literature review : 1) work accidents ; 2) commuting accidents such as car accidents that occur on the way to and from work ; and 3) attendance management at work (i.e., absenteeism, tardiness, and unscheduled early departure). These cognitive and behavioral consequences of shift work were also found to be associated with sleep disorders in shift workers. Thus, improvements in the shift work system are necessary in order to enhance workers' health conditions, work productivity, and safety.
Absenteeism ; Cognition ; Efficiency ; Fatigue ; Sleep Initiation and Maintenance Disorders ; Sleep Wake Disorders ; Transportation