Amyloid-beta Pathology in C. elegans: Neuronal Seeds of Pathogenicity

This lecture presents a novel C. elegans model for studying Amyloid-beta pathology in Alzheimer's Disease. The model employs sub-stoichiometric labelling and fluorescence microscopy to analyze age-dependent aggregation of Amyloid-beta. The expression of Amyloid-beta shortens lifespan, reduces offspring viability, and leads to paralysis. The lecture identifies specific neurons as early seeds of pathogenicity, showing defects in chemotaxis, pathogen avoidance, and neurodegeneration. Cell-type specific knockdown of Amyloid-beta rescues phenotypes, delaying aggregation and toxicity. The model differs from previous ones by including untagged Amyloid-beta, crucial for aggregation and toxicity. The lecture concludes with insights into the vulnerability of cholinergic IL2 neurons to Amyloid-beta aggregation.