Genetic and Neuropathologic Underpinnings of Sex Differences in Lewy Body Dementias

路易体痴呆性别差异的遗传和神经病理学基础

基本信息

批准号：
10650344
负责人：
ECE BAYRAM
金额：
$ 12.52万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10650344
关键词：
Acceleration Affect Alzheimer&apos s Disease Alzheimer&apos s disease pathology Award Big Data Bioinformatics Biological Markers Body Burden Brain California Clinic Clinical Clinical Research Clinical Trials Cognition Cognitive Data Data Set Dementia Dementia with Lewy Bodies Development Diagnosis Doctor of Philosophy Elderly Endosomes Five-Year Plans Foundations Frequencies Functional disorder Funding Future Genetic Genetic Risk Genomics Goals Heterogeneity Hippocampus Impaired cognition Individual Institution Leadership Lewy Bodies Lewy Body Dementia Lewy body pathology Life Medial Medicine Mentors Modeling Movement Disorders National Institute of Neurological Disorders and Stroke Neocortex Nerve Degeneration Neurodegenerative Disorders Neurologist Neuropsychology Parkinson Disease Parkinsonian Disorders Pathologic Pathologist Pathology Pathway interactions Patient Selection Patients Phase Phenotype Positioning Attribute Positron-Emission Tomography Prevalence Productivity Recording of previous events Reporting Research Research Personnel Research Project Grants Research Training Resources Salmon Sampling Scientist Senile Plaques Series Sex Differences Statistical Data Interpretation Symptoms Temporal Lobe Training Translational Research United States National Institutes of Health Universities Visual Hallucination Woman Work alpha synuclein career clinical diagnosis clinical diagnostics clinical phenotype clinical predictors cohort dementia risk diagnosis standard diagnostic accuracy disease phenotype experience genetic predictors genetic risk factor genetic variant genome sequencing improved men morphogens neocortical neurodegenerative dementia neuroimaging neuropathology non-demented precision medicine predictive modeling public-private partnership regional difference risk variant sex skill acquisition skills success tau Proteins whole genome

项目摘要

PROJECT SUMMARY Sex differences are commonly reported in Lewy body dementia, although the reasons are unknown. Phenotypic differences can be described by differences in the pathology and can be associated with differences in genetic risk loci. We hypothesize that Alzheimer's disease-related genetic risk factors will be associated with higher dementia risk in women with Lewy body dementia, given the higher likelihood of Alzheimer's co-pathology in women. However, even for women with pure Lewy body pathology, Alzheimer's phenotype is more common than Lewy body dementia phenotype, indicating sex differences for clinicopathologic correlations. This may be due to differences in regional pathology burden for men and women. Specific regional Lewy body and Alzheimer's pathology burden have been associated with different symptoms; and we hypothesize that men will have more neocortical Lewy body burden and women will have more pathology burden in the medial temporal lobe given the more common Alzheimer's phenotype in women. As Alzheimer's disease is the most common misdiagnosis for patients with Lewy body dementia, we will also develop sex-specific models with clinical and genetic variables to clinically differentiate Lewy body and Alzheimer's pathology. These findings will improve our understanding of the etiopathogenesis of Lewy body dementia, assist with patient selection for future clinical trials in both Lewy body dementia and Alzheimer's disease, and provide targets for precision medicine in these neurodegenerative dementias. The candidate is an Assistant Project Scientist (a mentored position) at the University of California San Diego. She has an MD and a PhD with prior training in neurodegenerative disorders, neuropsychology, and neuroimaging. She has a history of productivity, having conducted translational and clinical research in movement disorders, recently focusing on sex differences in Parkinsonian disorders. She is committed to a research career in translational research and proposes a comprehensive five-year plan of research and training to acquire skills in 1) genetic and genomic analysis, 2) interpreting neuropathological data, 3) performing statistical analyses with big data. During the award period, Dr. Bayram will build collaborative relationships with experts in the field of genetics, neuropathology, and bioinformatics to support her work as an independent researcher. This award will also support Dr. Bayram's professional development including training for grantsmanship, leadership, and administrative skills. Dr. Bayram will meet her goals under the guidance of a mentoring team including Dr. Irene Litvan (primary mentor), a world-renowned expert in cognitive decline in Parkinsonian disorders, Dr. Sonja Scholz (co-mentor, neurologist-neurogeneticist at NINDS), Dr. Ali Torkamani (bioinformatics mentor), Dr. David Salmon (neuropsychology mentor), Dr. Dennis Dickson (advisor, pathologist), Dr. Owen Ross (advisor, geneticist) and Dr. Abraham Palmer (advisor, geneticist), all of whom are well-established and NIH-funded researchers.

项目概要路易体痴呆症中常见性别差异，但原因尚不清楚。表型差异可以通过病理学差异来描述，并且可以与遗传风险位点的差异。我们假设与阿尔茨海默病相关的遗传风险因素是路易体痴呆症女性患痴呆症的风险较高，因为患路易体痴呆症的可能性较高女性阿尔茨海默病的共同病理学。然而，即使对于具有纯路易体病理学的女性，阿尔茨海默病表型比路易体痴呆表型更常见，表明性别差异用于临床病理相关性。这可能是由于男性和女性的区域病理负担存在差异。女性。特定区域路易体和阿尔茨海默病病理负担与不同的症状;我们假设男性将有更多的新皮质路易体负担，而女性将有更多的新皮质路易体负担考虑到阿尔茨海默病表型更常见，内侧颞叶的病理负担更大女性。由于阿尔茨海默病是路易体痴呆患者最常见的误诊，我们还将开发具有临床和遗传变量的性别特异性模型，以在临床上区分路易身体和阿尔茨海默病病理学。这些发现将提高我们对疾病发病机制的理解路易体痴呆，协助选择未来路易体痴呆和路易体痴呆临床试验的患者阿尔茨海默病，并为这些神经退行性痴呆症的精准医疗提供了靶点。该候选人是加州大学圣保罗分校的助理项目科学家（受指导的职位）迭戈.她拥有医学博士和博士学位，之前接受过神经退行性疾病、神经心理学和神经退行性疾病方面的培训。神经影像学。她有着高效的历史，曾在以下领域进行过转化和临床研究：运动障碍，最近关注帕金森病的性别差异。她致力于一个转化研究的研究生涯，并提出了一个全面的五年研究和计划培训以获得以下方面的技能：1) 遗传和基因组分析，2) 解释神经病理学数据，3) 利用大数据进行统计分析。在颁奖期间，Bayram 博士将建立合作关系与遗传学、神经病理学和生物信息学领域的专家的关系，以支持她的工作独立研究员。该奖项还将支持拜拉姆博士的专业发展，包括资助技巧、领导力和管理技能的培训。 Bayram 博士将在以下条件下实现她的目标包括世界知名专家 Irene Litvan 博士（主要导师）在内的导师团队的指导帕金森病认知能力下降，Sonja Scholz 博士（联合导师、神经学家、神经遗传学家） NINDS）、Ali Torkamani 博士（生物信息学导师）、David Salmon 博士（神经心理学导师）、Dr. Dennis Dickson（顾问、病理学家）、Owen Ross 博士（顾问、遗传学家）和 Abraham Palmer 博士（顾问、遗传学家），他们都是知名且由 NIH 资助的研究人员。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci.

对路易体痴呆症患者 X 染色体的遗传分析指定了新的风险位点。

DOI：
发表时间：
2024-02-20
期刊：
影响因子：
0
作者：
Bayram, Ece;Reho, Paolo;Litvan, Irene;International LBD Genomics Consortium;Ding, Jinhui;Gibbs, J Raphael;Dalgard, Clifton L;Traynor, Bryan J;Scholz, Sonja W;Chia, Ruth
通讯作者：
Chia, Ruth