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NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 1/2018

01-03-2018 | Original Paper

Differential Binding of Human ApoE Isoforms to Insulin Receptor is Associated with Aberrant Insulin Signaling in AD Brain Samples

Authors: Elizabeth S. Chan, Christopher Chen, Tuck Wah Soong, Boon-Seng Wong

Published in: NeuroMolecular Medicine | Issue 1/2018

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Abstract

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), where inheritance of this isoform predisposes development of AD in a gene dose-dependent manner. Although the mode of action of ApoE4 on AD onset and progression remains unknown, we have previously shown that ApoE4, and not ApoE3 expression, resulted in insulin signaling deficits in the presence of amyloid beta (Aβ). However, these reports were not conducted with clinical samples that more accurately reflect human disease. In this study, we investigated the effect of ApoE genotype on the insulin signaling pathway in control and AD human brain samples. We found that targets of the insulin signaling pathway were attenuated in AD cases, regardless of ApoE isoform. We also found a decrease in GluR1 subunit expression, and an increase NR2B subunit expression in AD cases, regardless of ApoE isoform. Lastly, we observed that more insulin receptor (IR) was immunoprecipitated in control cases, and more Aβ was immunoprecipitated with AD cases. But, when comparing among AD cases, we found that more IR was immunoprecipitated with ApoE3 than ApoE4, and more Aβ was immunoprecipitated with ApoE4 than ApoE3. Our results suggest that the difference in IR binding and effect on protein expression downstream of the IR may affect onset and progression of AD.
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Metadata
Title
Differential Binding of Human ApoE Isoforms to Insulin Receptor is Associated with Aberrant Insulin Signaling in AD Brain Samples
Authors
Elizabeth S. Chan
Christopher Chen
Tuck Wah Soong
Boon-Seng Wong
Publication date
01-03-2018
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 1/2018
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-018-8480-3

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