Research Paper Volume 13, Issue 9 pp 12410—12430

Distinct fiber-specific white matter reductions pattern in early- and late-onset Alzheimer’s disease

Xiao Luo1, *, , Shuyue Wang1, *, , Yeerfan Jiaerken1, , Kaicheng Li1, , Qingze Zeng1, , Ruiting Zhang1, , Chao Wang1, , Xiaopei Xu1, , Dan Wu2, , Peiyu Huang1, #, , Minming Zhang1, #, , Alzheimer’s Disease Neuroimaging Initiative (ADNI) ,

  • 1 Department of Radiology, The 2nd Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
  • 2 Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China
* Equal contribution
# Joint senior author

Received: October 7, 2020       Accepted: February 8, 2021       Published: April 30, 2021
How to Cite

Copyright: © 2021 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: The underlying white matter impairment in patients with early and late-onset Alzheimer’s disease (EOAD and LOAD) is still unclear, and this might due to the complex AD pathology.

Methods: We included 31 EOAD, 45 LOAD, and 64 younger, 46 elder controls in our study to undergo MRI examinations. Fiber density (FD) and fiber bundle cross-section (FC) were measured using fixel-based analysis based on diffusion weighted images. On whole brain and tract-based level, we compared these parameters among different groups (p<0.05, FWE corrected). Moreover, we verified our results in another independent dataset using the same analyses.

Results: Compared to young healthy controls, EOAD had significantly lower FD in the splenium of corpus callosum, limbic tracts, cingulum bundles, and posterior thalamic radiation, and higher FC in the splenium of corpus callosum, dorsal cingulum and posterior thalamic radiation. On the other hand, LOAD had lower FD and FC as well. Importantly, a similar pattern was found in the independent validation dataset. Among all groups, both the FD and FC were associated with cognitive function. Furthermore, FD of fornix column and body, and FC of ventral cingulum were associated with composite amyloid and tau level (r=-0.34 and -0.53, p<0.001) respectively.

Conclusions: EOAD and LOAD were characterized by distinct white matter impairment patterns, which may be attributable to their different neuropathologies.


FD: fiber density; FC: fiber bundle cross-section; FDC: fiber density and bundle cross-section; EOAD: early-onset Alzheimer's disease; LOAD: late-onset Alzheimer's disease; YHC: young healthy controls; OHC: old healthy controls.