Document Type

Article

Publication Date

12-2020

Publication Source

iScience

Abstract

To understand the progression of Alzheimer's disease, studies often rely on ectopic expression of amyloid-beta 42 (Aβ42) throughout an entire tissue. Uniform ectopic expression of Aβ42 may obscure cell-cell interactions that contribute to the progression of the disease. We developed a two-clone system to study the signaling cross talk between GFP-labeled clones of Aβ42-expressing neurons and wild-type neurons simultaneously generated from the same progenitor cell by a single recombination event. Surprisingly, wild-type clones are reduced in size as compared with Aβ42-producing clones. We found that wild-type cells are eliminated by the induction of cell death. Furthermore, aberrant activation of c-Jun-N-terminal kinase (JNK) signaling in Aβ42-expressing neurons sensitizes neighboring wild-type cells to undergo progressive neurodegeneration. Blocking JNK signaling in Aβ42-producing clones restores the size of wild-type clones.

ISBN/ISSN

2589-0042

Document Version

Published Version

Comments

Published under a Creative Commons Attribution license (CC-BY) 4.0.

DOI: https://doi.org/10.1016/j.isci.2020.101823

Publisher

Elsevier

Volume

23

Issue

12

Keywords

Cell Biology, Molecular Biology, Neuroscience

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