Nearly all people with Down Syndrome will develop Alzheimer’s Dementia neuropathology by age 50, often asymptomatically. In this work, diffusion tensor imaging (DTI) was used to characterize white matter (WM) tract microstructure in thirty-three non-demented participants with Down Syndrome. Amyloid plaque burden was assessed using PET imaging with C-11 PiB. DTI measures were used to compare WM microstructure in DS individuals with high amyloid burden (PiB+) versus individuals with low amyloid burden (PIB-). PIB+ adults demonstrated significantly increased mean diffusivity and decreased fractional anisotropy in several bilateral WM regions. These findings are consistent of signs of WM degeneration.