Antemortem White Matter Integrity Quantification from DTI and Relationship with Postmortem TDP-43

DTI 死前白质完整性定量及其与死后 TDP-43 的关系

基本信息

批准号：
10767777
负责人：
Ashley Heywood
金额：
$ 4.39万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
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：
2022-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10767777
关键词：
Affect Alzheimer&apos s Disease Amygdaloid structure Amyloid Anisotropy Area Autopsy Axon Biological Markers Brain Brain region Cerebrovascular Disorders Characteristics Cognition Cognitive Cohort Studies Communication Communities Computing Methodologies Data Dementia Dimensions Disease Disease Progression Distal Elderly Fiber Frontotemporal Lobar Degenerations Goals Heterogeneity Hippocampus Impaired cognition Internal Capsule Length Lewy body pathology Location Longitudinal cohort study Measures Mediating Mediation Methods Nerve Degeneration Neuroanatomy Neurobehavioral Manifestations Neurobiology Neurodegenerative Disorders Neurons Pathogenesis Pathologic Pathology Pattern Persons Pontine structure Population Process Research Research Personnel Role Sampling Shapes Stereotyping Structure Syndrome Therapeutic Agents Variant brain behavior burden of illness entorhinal cortex global health improved in vivo neuroimaging neuropathology potential biomarker protein TDP-43 tau Proteins white matter

项目摘要

Project Summary/Abstract Dementia syndromes are global health concerns affecting more than 55 million people worldwide, with an estimated 10 million new cases each year. Without a cure or therapeutic agents to stop the progression of disease, dementia remains a devastating illness which requires significant exploration. White matter microstructure is significantly affected within dementia, however, the relationship between underlying disease and microstructural integrity is poorly understood. Indeed, understanding neurobiological basis underlying cognitive decline in neurodegenerative disease remains an unmet challenge. There is a dearth of research on the relationship between antemortem brain characteristics and postmortem disease burden. TAR DNA-binding protein 43 (TDP-43) proteinopathy is a common feature of many neurodegenerative diseases, is known to affect white matter structural integrity, and needs to be explored in-vivo. While in addition to neuronal pathology, TDP- 43 is also highly involved in white matter and therefore, studying the relationships between TDP-43 and white matter structural integrity can allow for a better understanding of the neurodegenerative process. Utilizing a community-based sample of older adults from two cohort studies from the Rush Alzheimer’s Disease Center, I plan to measure the relationship between postmortem TDP-43 pathology and spatial antemortem white matter structural integrity and additionally explore its effect on cognition. Traditional measures of white matter integrity assume the entire tract to maintain similar characteristics, however, advanced computational research has identified that white matter integrity varies in stereotyped patterns along the tract. By studying the relationship between postmortem TDP-43 burden and spatial patterns of antemortem white matter integrity, we can assess localized white matter integrity as it relates to disease burden. I will then explore the association of white matter integrity and cognition through correlation and mediation analysis. No previous research has utilized postmortem neuropathological burden quantification to measure disease effects on in-vivo spatial white matter integrity. By exploring the relationship of postmortem quantification of TDP-43 burden and antemortem white matter structural integrity, we may enhance our understanding of the role of disease within the neurodegenerative process. Future research can expand this research to be used as a potential noninvasive, readily available, antemortem biomarker indicative of postmortem disease.

项目概要/摘要痴呆症综合症是全球健康问题，影响着全世界超过 5500 万人，其中估计每年有 1000 万新病例没有治愈方法或治疗药物来阻止病情进展。疾病，痴呆症仍然是一种毁灭性的疾病，需要对白质进行大量研究。痴呆症的微观结构受到显着影响，然而，基础疾病之间的关系事实上，人们对微观结构完整性知之甚少，对神经生物学基础的了解也很少。神经退行性疾病的认知能力下降仍然是一个尚未解决的挑战，目前还缺乏相关研究。生前大脑特征与死后疾病负担之间的关系。蛋白 43 (TDP-43) 蛋白病是许多神经退行性疾病的共同特征，已知会影响白质结构完整性，需要在体内进行探索，而除了神经元病理学之外，TDP- 43 也高度参与白质，因此，研究 TDP-43 和白质之间的关系物质结构完整性可以更好地理解神经退行性过程。来自拉什阿尔茨海默病中心的两项队列研究的基于社区的老年人样本，I 计划测量死后 TDP-43 病理学与空间死前白质之间的关系结构完整性，并进一步探讨其对认知的影响。白质完整性的传统测量。假设整个区域保持相似的特征，然而，先进的计算研究已经通过研究这种关系，发现白质完整性在沿着该束的刻板模式中有所不同。在死后 TDP-43 负担和死前白质完整性的空间模式之间，我们可以评估局部白质完整性，因为它与疾病负担有关，然后我将探讨白质的关联。通过相关性和中介分析来评估完整性和认知。以前没有研究利用事后分析。神经病理学负担量化，以测量疾病对体内空间白质完整性的影响。探索死后 TDP-43 负荷定量与死前白质结构的关系完整性，我们可以增强我们对疾病在未来神经退行性过程中的作用的理解。研究可以扩展这项研究，使其用作潜在的非侵入性、现成的、生前检查死后疾病的生物标志物指标。