Investigation of the Influence of Nudtl 9 and Dpp 7 Genes on Alzheimer's Disease Progression

Brianna Gurdon

Document Type

Article

Publication Date

Summer 2018

JAX Location

In: Student Reports, Summer 2018, The Jackson Laboratory

Abstract

Alzheimer's disease is a neurodegenerative disease influenced by a variety of genetic factors that affect the onset and progression of cognitive and pathological disease-related symptoms. Using a panel of genetically diverse transgenic mice that harbor dominantly-inherjted familial Alzheimer's Disease (FAD) mutations, Nudtl 9 and Dpp 7 were identified as genes that likely modify the effect of FAD mutations on the age at onset (AAO) and progression of AD. In order to test the hypothesis that Nudtl 9 and/or Dpp7 are directly involved in modulation of symptom onset and cognitive functioning, gene therapy tools were administered to drive the overexpression of Nudtl 9 or Dpp7 in the hippocampus and the functional effect on AAO and disease progression was assessed using a battery of cognitive tests. The efficacy of gene manipulation was evaluated using qPCR, Western Blot, and i1rununohistochemistry analysis. Overexpression of these genes resulted in a significant increase of Nudtl 9 expression at the RNA level (but not the protein level), while significant increases in Dpp7 expression were seen at the RNA and protein levels. Combined analysis of the molecular and behavioral results revealed that the perforn1ed overexpression of Dpp7 was sufficient to en11ance memory performance in AD mouse models, implicating this gene in the modification of symptoms and higltlighting it as a possible therapeutic target for AD.

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