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

项目摘要/摘要 痴呆症是影响全球5500多万人的全球健康问题， 据估计，每年新增病例为1000万例。如果没有治愈或治疗药物来阻止疾病的发展 痴呆症仍然是一种毁灭性的疾病，需要进行大量的探索。白质 微观结构在痴呆症中受到显著影响，然而，基础疾病之间的关系 人们对微观结构的完整性知之甚少。的确，了解潜在的神经生物学基础 神经退行性疾病的认知衰退仍然是一个尚未满足的挑战。对……的研究很少。 死前脑特征与死后疾病负担的关系TAR DNA结合 蛋白43(TDP-43)蛋白病是许多神经退行性疾病的共同特征，已知影响 白质结构的完整性，需要在体内进行探索。而除了神经元病理，TDP- 43也高度参与白质，因此，研究TDP-43和白质之间的关系 物质结构的完整性可以更好地理解神经退化过程。利用一种 来自拉什阿尔茨海默病中心的两项队列研究的社区老年人样本，即 计划测量死后TDP-43病理与空间生前白质的关系 结构完整性，并另外探讨其对认知的影响。脑白质完整性的传统测量方法 然而，假设整个过程都保持类似的特征，高级计算研究已经 发现白质的完整性沿束以刻板印象的模式变化。通过研究两者之间的关系 在死后TDP-43负荷和生前白质完整性的空间模式之间，我们可以评估 局部性白质完整性与疾病负担相关。然后我将探索白质与 通过关联和中介分析的完整性和认知性。以前的研究都没有利用身体解剖 神经病理负荷量化以衡量疾病对体内空间白质完整性的影响。通过 TDP-43负荷死后量化与生前脑白质结构关系的探讨 诚信，我们可能会加强我们对疾病在神经退化过程中的作用的理解。未来 研究可以将这项研究扩展为潜在的非侵入性、容易获得的临终前研究 指示死后疾病的生物标志物。

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.