Genetic dissection of dementia

痴呆症的基因剖析

基本信息

批准号：
10412678
负责人：
Kyung-An Han
金额：
$ 15.3万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-13 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10412678
关键词：
Acetylcholine Address Affect Age Alleles Alzheimer&apos s Disease Alzheimer&apos s disease related dementia American Amyloid Animal Model Biomedical Research Candidate Disease Gene Caregivers Chronic Disease Communities Consumption DNA Sequence Alteration Deletion Mutation Dementia Development Disease Dissection Drosophila genus Drosophila melanogaster Economic Burden Elderly Enzymes Etiology Gene Expression Gene Mutation Genes Genetic Genetic Crosses Genetic Screening Goals Hispanic Populations Insertion Mutation Intercistronic Region Introns Knowledge Link Mammals Measures Memory Memory Loss Mutation Nerve Degeneration Neurosciences Research Oxidative Stress Pathogenicity Point Mutation Prevalence Prevention Process Progressive Disease RNA Interference Research Research Training Rest Rodent Model Role Sleep Deprivation Societies Students Symptoms Synapses Tauopathies Testing Therapeutic Time Training and Education Transgenic Organisms X Chromosome age related biological research caucasian American combat conditioning cost cost effective dopaminergic neuron endophenotype executive function fly gene discovery gene function genetic risk factor genome wide association study genomic locus health economics human old age (65+)innovation insight mutant non-genetic relating to nervous system screening social factors social stress tau aggregation tool

项目摘要

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.

项目摘要本研究的主要目标是确定具有功能意义的遗传风险因素模式生物果蝇中的痴呆。痴呆症的关键因素是年龄依赖性神经变性削弱执行功能（例如抑制控制）和记忆。大多数痴呆症研究都集中在记忆丧失上，这是痴呆症的一个突出症状 AD——最常见的痴呆类型。虽然动物模型提供了重要的见解记忆丧失的机制，自该研究以来，它们在痴呆症基因发现中的效用有限记忆力减退是一件费时又费力的事情。执行缺陷是早期的主要症状 AD 阶段和相关痴呆症尚未得到充分研究。我们通过以下方式克服这些限制研究抑制控制缺陷作为痴呆的内表型以发现痴呆基因，创新。我们的方法是对遗传位点进行公正的筛选以年龄依赖性方式导致功能失调的抑制控制，无论有或没有非遗传风险因素。在这个提案中，我们还将检验遗传和非遗传性的假设遗传风险因素相互作用对痴呆症的影响比单独的遗传因素更大。果蝇易于处理学生研究培训和教育，因为它易于处理，允许轻松应用最先进的工具和方法，并且具有成本效益和时间效益。有目前 UTEP 没有其他关于痴呆症的生物学研究。痴呆症患病率是西班牙裔美国人的比例不成比例地高于美国白人，因此这项研究不仅会促进与我们的学生和社区相关的研究，同时也增加了西班牙裔的代表性目前神经科学研究的水平极低。