摘要：SummaryTo 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.Graphical AbstractDisplay OmittedHighlights•In the two-clone system a subset of neurons in a field expresses high levels of Aβ42•A genetic recombination event generates Aβ42-expressing (GFP +ve) and WT neurons•Surprisingly, WT neurons die prior to widespread death of Aβ42-expressing neurons•Higher levels of JNK signaling in Aβ42-expressing cells causes death of WT neuronsCell Biology; Molecular Biology; Neuroscience
