Human amyloid-beta induces abnormal embryonic development and high embryonic lethality in <i>Caenorhabditis elegans</i>

Abstract The aggregation of amyloid-β (Aβ) proteins is widely recognized as a key pathological biomarker of Alzheimer’s Disease (AD); its physiological function, however, remains largely unknown. Previous research has suggested that Aβ may regulate human brain embryogenesis and embryonic development in zebrafish. In this study, we used a Caenorhabditis elegans model of AD to explore the physiological function of human Aβ during embryogenesis. Analysis of embryonic lethality using strains CL2120 (human Aβ expressing) and CL2122 (empty vector control) shows a high embryonic lethality rate (31%), mostly occurring between the end of gastrulation to the 1.5-fold stage. RNAi screening and transcriptome analysis revealed that a key HOX developmental gene, nob-1, and its upstream regulator, elt-1, are significantly overexpressed in CL2120. As nob-1 is heavily involved in posterior development at the end of gastrulation, our findings suggest that the elevated levels of ELT-1, induced by human Aβ expression, contribute to the observed high embryonic lethality. Taken together, our results indicate that Aβ proteins influence embryonic development by dysregulating key HOX genes.