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According to the amyloid theory of disease, Alzheimer’s disease results from the aggregation of Aβ fragments and the formation of detrimental amyloid plaques in the brains of patients. The production of toxic Aβ results from alternative cleavage of amyloid precursor protein (APP) by β-secretase and γ-secretase as opposed to cleavage by α-secretase. In the model organism, Danio rerio (zebrafish), the gene ADAM10a is homologous to human α-secretase. This study sought to assess the effects of knocking down ADAM10a in zebrafish in order to elucidate the role of this gene in Alzheimer’s pathology and the potential of zebrafish as an animal model for the disease. Previous results purport that ADAM10a to be necessary for embryogenesis and thus the effect of genetic knockdown post-gastrulation was ill-defined. By utilizing fluorescent morpholino knockdown techniques, ADAM10a knockdown embryos were shown to survive post-gastrulation. These findings suggest the possibility of assessing morphological effects of ADAM10a knockdown in zebrafish later in development, the association of these effects with Alzheimer’s disease pathology and ultimately defining the role ADAM10a in the amyloid theory of Alzheimer’s disease.
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Kelly, Taryn Leigh, "ADAM10a and Danio rerio: Towards a Model for Alzheimer’s Disease" (2015). Senior Projects Spring 2015. 259.
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