A novel Caenorhabditis elegans model of Alzheimer’s Disease

Abstract Background Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative disease, characterised by the presence of Aβ plaques and neurofibrillary tangles, mediating memory impairments due to loss of neurons and impairments in neuronal plasticity. The most common model to study the toxic effects of Aβ in AD are transgenic rodents. However, these animals develop cognitive impairments and suffer. Thus, to reduce and replace the rodent animals used to study these toxic effects, we are developing a C. elegans neuronal model of human Aβ 1‐42 with a posterior co‐injection marker to allow multi‐colour neuronal imaging without interference from the fluorescence of the co‐injection marker. To achieve this we generated a transcriptional reporter of the antimicrobial peptide gene clec‐60 , as the expression of this gene under normal conditions is solely in the posterior intestine. Method Constructs containing ultra pan‐neuronal Aβ reporter and the clec‐60p ::cemOrange co‐injection marker were generated via gateway cloning and micro‐injected into wild type C. elegans . To confirm expression of the co‐injection marker is restricted to posterior intestine confocal images were taken of the injected strains. To confirm presence of Aβ in the neurons, fixed C. elegans were antibody stained using the 4G8 primary and goat anti mouse 488 secondary antibody. Result We generated the Aβ strain with the clec‐60 fluorescent marker, however, upon expression of the human Aβ 1‐42 in the C. elegans nervous system we observed expression of the fluorescently tagged clec‐60 in the neurons. The presence of the Aβ in the neurons was confirmed with the antibody staining. Conclusion Expression of human Aβ 1‐42 changes and increases the expression of the innate immunity antimicrobial peptide clec‐60 indicating C. elegans perceive Aβ as a pathogen and elevate innate immune peptide upon its expression.