TY - JOUR T1 - Analysis of Neurons Created from Wild-Type and Alzheimer's Mutation Knock-In Embryonic Stem Cells by a Highly Efficient Differentiation Protocol JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8513 LP - 8525 DO - 10.1523/JNEUROSCI.23-24-08513.2003 VL - 23 IS - 24 AU - Yoichiro Abe AU - Keisuke Kouyama AU - Taisuke Tomita AU - Yusuke Tomita AU - Norimitsu Ban AU - Mikiro Nawa AU - Masaaki Matsuoka AU - Takako Niikura AU - Sadakazu Aiso AU - Yoshiko Kita AU - Takeshi Iwatsubo AU - Ikuo Nishimoto Y1 - 2003/09/17 UR - http://www.jneurosci.org/content/23/24/8513.abstract N2 - It is impossible to obtain and amplify live neurons from Alzheimer's disease (AD) patients. To establish the neurons harboring AD abnormality, we constructed mouse embryonic stem (ES) cells, in which the AD-causative V642I mutation was introduced to the endogenous amyloid precursor protein (APP) gene, in combination with a protocol to efficiently differentiate ES cells into postmitotic neurons without using a cell sorter. By this protocol, ES cells differentiated into >90% of the central type of adult postmitotic neurons. Neurons derived from V642I–APP knock-in ES cells were indistinguishable from wild-type ES-derived neurons, as determined by the expression of various markers for neuronal differentiation. Notably, V642I–APP knock-in ES cell-derived neurons exhibited significantly increased secretion of Aβ42 without AD-related hyperphosphorylation of tau, indicating that the direct output of the AD-causative mutation is increased Aβ42 secretion. In this study, we analyze created neurons with wild-type and AD genotypes and propose a new strategy for generating neurons for any dominantly inherited neurodegenerative diseases. The strategy can be applied to create human neurons with AD or any other neurodegenerative disease by using human ES cells. ER -