title: Alzheimer's in 3D culture: challenges and perspectives.
abstract: 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.
authors.affiliation: Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: D'Avanzo
authors.affiliation: Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Aronson
authors.affiliation: Biomedical Omics Group, Korea Basic Science Institute, Cheongju-si, Chungbuk, Republic of Korea.
authors.forename: Young Hye
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.affiliation: Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Doo Yeon
authors.initials: DY
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000473:pathology*
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: 3D culture; APP; Alzheimer's disease; human stem cell; presenelin