Lack of evidence of the interaction of the Aβ peptide with the Wnt signaling cascade in Drosophila models of Alzheimer's disease.
BACKGROUND
Alzheimer's disease (AD) is the leading form of dementia worldwide. The Aβ-peptide is believed to be the major pathogenic compound of the disease. Since several years it is hypothesized that Aβ impacts the Wnt signaling cascade and therefore activation of this signaling pathway is proposed to rescue the neurotoxic effect of Aβ.


RESULTS
Expression of the human Aβ42 in the Drosophila nervous system leads to a drastically shortened life span. We found that the action of Aβ42 specifically in the glutamatergic motoneurons is responsible for the reduced survival. However, we find that the morphology of the glutamatergic larval neuromuscular junctions, which are widely used as the model for mammalian central nervous system synapses, is not affected by Aβ42 expression. We furthermore demonstrate that genetic activation of the Wnt signal transduction pathway in the nervous system is not able to rescue the shortened life span or a rough eye phenotype in Drosophila.


CONCLUSIONS
Our data confirm that the life span is a useful readout of Aβ42 induced neurotoxicity in Drosophila; the neuromuscular junction seems however not to be an appropriate model to study AD in flies. Additionally, our results challenge the hypothesis that Wnt signaling might be implicated in Aβ42 toxicity and might serve as a drug target against AD.
Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne, 1005, Switzerland. anne-marie.luchtenborg@unil.ch.
Anne-Marie
AM
Lüchtenborg
Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne, 1005, Switzerland. vladimir.katanaev@unil.ch.
Vladimir L
VL
Katanaev
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000378:metabolism*; D005123:Eye / Q000473:pathology; D006801:Humans; D008136:Longevity; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D034622:RNA Interference; D060449:Wnt Signaling Pathway
D016229:Amyloid beta-Peptides