TY - JOUR
T1 - Human-induced pluripotent stem cells as a model for studying sporadic Alzheimer's disease
AU - Riemens, R J M
AU - Kenis, G
AU - van den Beucken, T
N1 - Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - The discovery of induced pluripotent stem cell (iPSC) technology has the potential to accelerate scientific research for Alzheimer's disease (AD). iPSCs are therefore increasingly considered for AD modeling and drug development. Nevertheless, most of the work conducted so far has mainly focused on iPSC models from patients with familial AD (fAD), while actually sporadic AD (sAD) is more prevalent and represents over 90% of the AD cases in the population. The development of more sAD models is therefore key for studying this multifactorial disorder. In fact, probing the unique genomes of sAD patients and their interaction with AD-associated environmental factors could contribute to a better understanding of this disease. However, initial iPSC-based models for sAD have shown a high degree of variability and inconsistencies in terms of AD hallmarks. In this review, we provide an overview of the studies that have been conducted for sAD so far. In addition, we critically assess important sources of variability related to the model in addition to those that might be explained by the heterogeneous nature of sAD. These considerations might aid in developing more consistent iPSC models of sAD, which could help in developing a better understanding of the molecular mechanisms underlying the disease.
AB - The discovery of induced pluripotent stem cell (iPSC) technology has the potential to accelerate scientific research for Alzheimer's disease (AD). iPSCs are therefore increasingly considered for AD modeling and drug development. Nevertheless, most of the work conducted so far has mainly focused on iPSC models from patients with familial AD (fAD), while actually sporadic AD (sAD) is more prevalent and represents over 90% of the AD cases in the population. The development of more sAD models is therefore key for studying this multifactorial disorder. In fact, probing the unique genomes of sAD patients and their interaction with AD-associated environmental factors could contribute to a better understanding of this disease. However, initial iPSC-based models for sAD have shown a high degree of variability and inconsistencies in terms of AD hallmarks. In this review, we provide an overview of the studies that have been conducted for sAD so far. In addition, we critically assess important sources of variability related to the model in addition to those that might be explained by the heterogeneous nature of sAD. These considerations might aid in developing more consistent iPSC models of sAD, which could help in developing a better understanding of the molecular mechanisms underlying the disease.
U2 - 10.1016/j.nlm.2020.107318
DO - 10.1016/j.nlm.2020.107318
M3 - (Systematic) Review article
C2 - 32977028
SN - 1074-7427
VL - 175
JO - Neurobiology of Learning and Memory
JF - Neurobiology of Learning and Memory
M1 - 107318
ER -