Genetic dissection of dementia
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Principal Investigator: Kyung-An Han Organization: UNIVERSITY OF TEXAS EL PASO Fiscal Year: 2024 Award: $153,500 Funding agency: National Institute of General Medical Sciences 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. Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><AD dementia><AD related dementia><ADRD><Acetylcholine><Address><Affect><Age><Aged 65 and Over><Alleles><Allelomorphs><Alzheimer Type Dementia><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimer's and related dementias><Alzheimer's disease and related dementia><Alzheimer's disease and related disorders><Alzheimer's disease or a related dementia><Alzheimer's disease or a related disorder><Alzheimer's disease or related dementia><Alzheimer's disease related dementia><Alzheimers Dementia><Amentia><American><Amyloid><Amyloid Substance><Animal Model><Animal Models and Related Studies><Biomedical Research><Candidate Disease Gene><Candidate Gene><Care Givers><Caregivers><Causality><Chronic Disease><Chronic Illness><Communities><Consumption><DA Neuron><DNA Alteration><DNA Sequence Alteration><DNA mutation><Deletion Mutation><Dementia><Development><Disease><Disorder><Dissection><Dopamine neuron><Drosophila><Drosophila genus><Drosophila melanogaster><Economic Burden><Education and Training><Elderly><Enzyme Gene><Enzymes><Etiology><Flies><GWA study><GWAS><Gene Alteration><Gene Expression><Gene Mutation><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic Crosses><Genetic Screening><Genetic defect><Genetic mutation><Genetic predisposing factor><Goals><Hispanic Populations><Hispanic group><Hispanic individual><Hispanic people><Hispanics><Insertion Mutation><Intercistronic Region><Intergenic Regions><Intervening Sequences><Introns><Knowledge><Link><Mammalia><Mammals><Measures><Memory><Memory Loss><Mutation><Nerve Degeneration><Neuron Degeneration><Neurosciences Research><Oxidative Stress><Pathogenicity><Point Mutation><Post-Transcriptional Gene Silencing><Posttranscriptional Gene Silencing><Prevalence><Prevention><Primary Senile Degenerative Dementia><Process><Progressive Disease><RNA Interference><RNA Silencing><RNAi><Research><Research Training><Rest><Risk Factors><Rodent Model><Role><Sequence Alteration><Sequence-Specific Posttranscriptional Gene Silencing><Sleep Deprivation><Societies><Students><Symptoms><Synapses><Synaptic><Tauopathies><Testing><Therapeutic><Time><Training and Education><X Chromosome><abnormally aggregated tau protein><above age 65><advanced age><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated><age associated neurodegeneration><age associated neurodegenerative disease><age associated neurodegenerative disorder><age correlated><age dependent><age dependent neurodegeneration><age dependent neurodegenerative condition><age dependent neurodegenerative disease><age dependent neurodegenerative disorder><age linked><age of 65 years onward><age related><age related neurodegeneration><age specific><age-driven neurodegenerative disorders><age-related neurodegenerative disease><age-related neurodegenerative disorder><aged 65 and greater><aged 65+><aged ≥65><ages><aging associated neurodegeneration><aging associated neurodegenerative disease><aging related neurodegeneration><aging related neurodegenerative disease><aging related neurodegenerative disorder><biological research><caucasian American><causation><chronic disorder><combat><conditioning><cost><cost effective><deficient sleep><developmental><discover genes><disease causation><dopaminergic neuron><endophenotype><executive control><executive function><filamentous tau inclusion><fly><fruit fly><gene discovery><gene function><gene locus><genetic locus><genetic risk factor><genome mutation><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><genomic alteration><genomic location><genomic locus><geriatric><health economics><human old age (65+)><inadequate sleep><inherited factor><innovate><innovation><innovative><insight><insufficient sleep><memory decline><microtubule associated protein tau aggregation><microtubule associated protein tau deposit><model of animal><model organism><mutant><neural><neural degeneration><neurodegeneration><neurodegenerative><neurological degeneration><neuronal degeneration><neuropathologic tau><neuropathological tau><non-genetic><nongenetic><old age><over 65 years><paired helical filament of tau><primary degenerative dementia><screening><screenings><self-aggregate tau><senile dementia of the Alzheimer type><senior citizen><sleep debt><sleep deficiency><sleep deficit><sleep insufficiency><sleep loss><social factors><social role><social stress><socially stressed><synapse><tau PHF><tau accumulation><tau aggregate><tau aggregation><tau associated neurodegeneration><tau associated neurodegenerative process><tau fibrillization><tau filament><tau induced neurodegeneration><tau mediated neurodegeneration><tau neurodegenerative disease><tau neurofibrillary tangle><tau neuropathology><tau oligomer><tau paired helical filament><tau polymerization><tau-tau interaction><tauopathic neurodegenerative disorder><tauopathy><tool><transgene expression><white American><whole genome association analysis><whole genome association studies><whole genome association study><τ aggregation><≥65 years>