Genetic dissection of dementia

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Project Abstract The major goal of this research is to identify the genetic risk factors with functional significance to dementia in the model organism Drosophila melanogaster. The key aspect of dementia is age- dependent neurodegeneration that cripples executive functions (e.g. inhibitory control) and memory. Most dementia studies have focused on memory loss, which is a prominent symptom of AD - the most common dementia type. While animal models have provided important insights into the mechanism for memory loss, their utility for dementia gene discovery is limited since the study of memory loss is time-consuming and laborious. Executive deficits are major symptoms in early stage AD and related dementias yet largely understudied. We overcome these limitations by studying inhibitory control deficit as a dementia endophenotype for the discovery of dementia genes, which is innovative. Our approach is to conduct an unbiased screen for the genetic loci causing dysfunctional inhibitory control in an age-dependent manner, with or without the non- genetic risk factors. In this proposal we will also test the hypothesis that the genetic and non- genetic risk factor interaction has a greater effect on dementia than a genetic factor alone. Drosophila is tractable for student research training and education as it is easy to handle, allows to readily apply state-of-the-art tools and approaches, and is cost-and time-effective. There is currently no other biological research on dementia at UTEP. Dementia prevalence is disproportionately higher in Hispanics than white Americans thus this study will not only promote research relevant to our students and community but also increase the representation of Hispanics in neuroscience research that is disproportionately low at present.