Fiber tract profiles of community dwelling older adults with LATE‐NC and associations with postmortem TDP‐43

• DOI: 10.1002/alz.094979
• Publication Date: 2025-01-09T10:21:58Z
• Authors: Ashley Heywood; Julie A. Schneider; David A. Bennett; Konstantinos Arfa...; Lei Wang

Abstract Background TAR DNA‐binding protein 43 (TDP‐43), has been shown to be involved in various neurodegenerative disorders involving axonal damage including ALS, FTLD, and LATE. Studying the relationships between postmortem TDP‐43 antemortem white matter (WM) structural integrity can allow for a better understanding of underlying neural mechanisms disease. Measures assume fiber bundles maintain similar characteristics along length tract, however, advanced computational research identified that varies stereotyped patterns tract. Methods In‐vivo diffusion‐weighted images were gathered on 1.5T scanner from subjects Religious Orders Study Rush Memory Aging Project. Tractography was conducted each subject using Mrtrix3 Automated Fiber Quantification (AFQ) used calculate fractional anisotropy (FA) tracts 20 major bundles. A semi‐quantitative rating severity assessed 5 brain regions. We utilized regression models relate disease FA at 100 nodes tract while controlling coexisting Alzheimer’s pathology demographics. Results The 63 91.2 (SD = 6.2) [range: 71.7‐103.6] years old death. Thirty‐eight percent had 36% cognitive changes before Overall, profiles revealed variation bundle. measuring relationship significant negative (FWE corrected‐p<0.05) unique portions left hippocampal cingulum. Conclusion Findings support current literature indicating does not follow uniform pattern older adults. Pathology reveal which have TDP‐43. Understanding these vulnerable regions will critical elucidating effect leading decline.