Pursuit of precision medicine: Systems biology approaches in Alzheimer\u27s disease mouse models.

Alzheimer\u27s disease (AD) is a complex disease that is mediated by numerous factors and manifests in various forms. A systems biology approach to studying AD involves analyses of various body systems, biological scales, environmental elements, and clinical outcomes to understand the genotype to phenotype relationship that potentially drives AD development. Currently, there are many research investigations probing how modifiable and nonmodifiable factors impact AD symptom presentation. This review specifically focuses on how imaging modalities can be integrated into systems biology approaches using model mouse populations to link brain level functional and structural changes to disease onset and progression. Combining imaging and omics data promotes the classification of AD into subtypes and paves the way for precision medicine solutions to prevent and treat AD

Investigation of the Influence of Nudtl 9 and Dpp 7 Genes on Alzheimer\u27s Disease Progression

Alzheimer\u27s 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\u27s 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