For the first time, we applied fixel-based analysis (FBA) to investigate fibre tract-specific WM changes in early-onset Alzheimer’s disease (EOAD) and late-onset AD (LOAD). To test the repeatability of the results, we repeated the analysis in two independent cohort. We demonstrated that EOAD in two cohorts had more widespread WM tracts loss than LOAD. The different FD extended from the limbic system to long posterior projection regions. Further, we found that FD, rather than FC, had a higher sensitivity in detecting WM loss of EOAD, and vice versa in LOAD. Results may provide clinical clues for early diagnosis of EOAD.