Analysis of Neurons Created from Wild-type and Alzheimer's Mutation Knock-in Embryonic Stem Cells by a Highly Efficient Differentiation Protocol

Overview

Journal J Neurosci

Specialty Neurology

Date 2003 Sep 19

PMID 13679420

Citations 7

Authors

Yoichiro Abe

Keisuke Kouyama

Taisuke Tomita

Yusuke Tomita

Norimitsu Ban

Mikiro Nawa

Masaaki Matsuoka

Takako Niikura

Sadakazu Aiso

Yoshiko Kita

Takeshi Iwatsubo

Ikuo Nishimoto

Affiliations

Soon will be listed here.

Abstract

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 Abeta42 without AD-related hyperphosphorylation of tau, indicating that the direct output of the AD-causative mutation is increased Abeta42 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.

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