Synergistic toxicity between tau and amyloid drives neuronal dysfunction and neurodegeneration in transgenic Caenorhabditis elegans

• DOI: 10.1002/alz.047426
• Publication Date: 2020-12-07T18:27:49Z
• Authors: Sarah J Benbow; Timothy J Strovas; Martin Darvas; Aleen Saxton; Brian C Kraemer
• Keywords: Tauopathy; Tau protein; Amyloid (mycology)

Abstract Background Aggregates of Aβ peptide and the microtubule‐associated protein tau are key molecular hallmarks Alzheimer's disease (AD). However, interaction between these two pathologies mechanisms underlying progression have remained unclear. Numerous failed clinical trials suggest necessity for greater mechanistic understanding in order to refine strategies therapeutic discovery development. Method To this end, we generated a transgenic Caenorhabditis elegans model expressing both human 1‐42 pan‐neuronally. We used behavioral, morphological biochemical assays assess pathological progression. Results observed exacerbated behavioral dysfunction age‐dependent neurodegenerative changes Aβ;tau animals. Further, occurred animals at levels than worms harboring either or transgene alone interestingly without expression, phosphorylation aggregation. Functional were partially rescued with introduction genetic suppressor pathology. Conclusion Taken together, data herein support synergistic role driving neuronal seen AD. Additionally, believe that utilization genetically tractable C. will provide resource dissecting AD