Fig. 1: Neurons have varied susceptibility to human Aβ42 deposition in novel Drosophila melanogaster model.

A Diagram showing the life cycle of Drosophila melanogaster. Translucency of the Drosophila during the three developmental stages of embryo, larva and pupa, make this model ideal for unintrusive live imaging at these stages. B Images showing the expression of the mKate2 fluorescent protein being driven by a neuronal nSyb driver. Incorporation of mKate2 into our Aβ plasmid allows us to visualise the neurons that are secreting hAβ42 in the translucent Drosophila embryo at stage E15 [Left], larva at stage L2 [Middle] and pupa at stage P13 [Right]. C Survival curves of Drosophila expressing no Aβ and Drosophila secreting hAβ42 neuronally using an nSyb driver. D Image of Drosophila embryo at stage E15 secreting hAβ42 neuronally [Grey] using an nSyb driver, fixed and stained with Aβ42 primary antibody and Alexa 488 secondary antibody [Green]. Boxed region highlights the varied accumulation of secreted hAβ42 found at the neuronal soma of different neurons in the CNS with inset enlarged in below panels as hAβ42-releasing neurons [Left, Grey], Aβ42 [Middle, Green] and these images overlaid [Right, Grey and Green]. E Image showing the dissected CNS from a late third instar Drosophila larva (L3) secreting hAβ42 neuronally [Grey] using an nSyb driver, fixed and stained with Aβ42 primary antibody and Alexa 488 secondary antibody [Green]. Pink boxed region highlights continued variation in the accumulated secreted hAβ42 found at the neuronal soma of different neurons in the CNS with inset of Aβ42 staining overlaid with hAβ42-releasing neurons enlarged in pink boxed panel below [Left, Grey and Green]. Blue boxed region highlights punctate-like staining of hAβ42 at certain neuronal axons in the CNS neuropil with inset of Aβ42 staining overlaid with hAβ42-releasing neurons enlarged in blue boxed panel below [Middle, Grey and Green]. Orange boxed region highlights plaque-like staining of hAβ42 found lodged in folds of the brain surface in some third instar larvae with inset enlarged in orange boxed panel below [Right, Green Aβ42 and Grey hAβ42-releasing neurons]. F Image showing the right hemisphere of a dissected CNS from Drosophila pupa at stage P13 secreting hAβ42 neuronally [Grey] using an nSyb driver, fixed and stained with Aβ42 primary antibody and Alexa 488 secondary antibody [Green]. Pink boxed region highlights continued variation in the accumulated secreted hAβ42 found at the neuronal soma of different neurons in the CNS with inset of Aβ42 staining overlaid with hAβ42-releasing neurons enlarged in pink boxed panel below [Left, Grey and Green]. Lower middle panel shows the same CNS at a different depth where plaque-like staining of Aβ42 is visible lodged in folds at the brain surface, inset enlarged in blue boxed panel beside [Right, Green Aβ42 and Grey hAβ42-releasing neurons].