# Antemortem White Matter Integrity Quantification from DTI and Relationship with Postmortem TDP-43 > **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2022 · $42,385 ## Abstract 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. ## Key facts - **NIH application ID:** 10537812 - **Project number:** 1F31AG079630-01 - **Recipient organization:** NORTHWESTERN UNIVERSITY - **Principal Investigator:** Ashley Heywood - **Activity code:** F31 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $42,385 - **Award type:** 1 - **Project period:** 2022-09-01 → 2024-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10537812 ## Citation > US National Institutes of Health, RePORTER application 10537812, Antemortem White Matter Integrity Quantification from DTI and Relationship with Postmortem TDP-43 (1F31AG079630-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10537812. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*