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Familial Alzheimer's disease modelling using induced pluripotent stem cell technology

World Journal of Stem Cells 2014年第2期6卷 239-247页

作者： lisa mohamet Natalie J Miazga Christopher M Ward Stem Cell Biology Group Core Technology FacilityFaculty of Human and Medical SciencesThe University of Manchester

Alzheimer’s disease(AD)is a progressive neurodegenerative disease in which patients exhibit gradual loss of memory that impairs their ability to learn or carry out daily tasks.Diagnosis of AD is difficult,particularly in early stages of the disease,and largely consists of cognitive assessments,with only one in four patients being correctly diagnosed.Development of novel therapeutics for the treatment of AD has proved to be a lengthy,costly and relatively unproductive process with attrition rates of>90%.As a result,there are no cures for AD and few treatment options available for patients.Therefore,there is a pressing need for drug discovery platforms that can accurately and reproducibly mimic the AD phenotype and be amenable to high content screening applications.Here,we discuss the use of induced pluripotent stem cells(iPSCs),which can be derived from adult cells,as a method of recapitulation of AD phenotype in vitro.We assess their potential use in high content screening assays and the barriers that exist to realising their full potential in predictive efficacy,toxicology and disease modelling.At present,a number of limitations need to be addressed before the use of iPSC technology can be fully realised in AD therapeutic applications.However,whilst the use of AD-derived iPSCs in drug discovery remains a fledgling field,it is one with immense potential that is likely to reach fruition within the next few years.

关键词： Human induced pluripotent stem cells Alzheimer’s disease Neurodegenerative diseases Highthroughput screening assays Cholinergic neurons Drug discovery Stratified medicine

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