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Updated: Mar 29, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Insights into White Matter Damage in Alzheimer's Disease: From Postmortem to in vivo Diffusion Tensor MRI Studies
Francesca Caso1, Federica Agosta, Massimo Filippi
1Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Background:
Alzheimer's disease (AD) has traditionally been considered a disease of the gray matter (GM). However, several pathological and neuroimaging studies provided evidence of white matter (WM) abnormalities in this disease. The advent of diffusion tensor (DT) MRI allowed researchers to study in vivo cerebral WM abnormalities in AD, including the earliest stage of the disease and its atypical variants.
Objective:
To provide a concise overview of the main neuropathological and DT MRI studies that explored WM damage in AD providing new insights into the underlying pathophysiological mechanisms.
Results:
Neuropathological studies revealed that GM and WM changes did not concur regionally in many areas, where well-preserved GM often lay over severely changed WM also in nondemented subjects with an underlying AD pathology. DT MRI studies confirmed in vivo a severe WM involvement in classical and atypical AD variants and in the prodromal stage of the disease. Microstructural WM damage was severer and more distributed than expected on the basis of cortical atrophy in all clinical AD phenotypes.
Conclusions:
AD is characterized by a relevant involvement of the WM as demonstrated by postmortem and in vivo evidence. WM microstructural damage in AD is not always secondary to neuronal loss, suggesting a role of other pathological mechanisms such as prion-like propagation of altered proteins or neuroinflammation. DT MRI offers new insight into AD pathophysiology and, more importantly, new possible targets for future experimental therapies.
Insights
Alzheimer's disease involves significant white matter damage, not just gray matter. Diffusion tensor MRI reveals this damage is widespread and occurs early, suggesting new therapeutic targets.
Area of Science:
- Neuroscience
- Neuropathology
- Radiology
Background:
- Alzheimer's disease (AD) traditionally focused on gray matter (GM) pathology.
- Emerging evidence highlights white matter (WM) abnormalities in AD.
- Diffusion tensor (DT) MRI enables in vivo study of WM changes in early and atypical AD.
Purpose of the Study:
- To review neuropathological and DT MRI studies on WM damage in AD.
- To offer insights into AD pathophysiological mechanisms.
Main Methods:
- Analysis of postmortem neuropathological findings.
- Review of in vivo diffusion tensor (DT) MRI studies in AD patients.
Main Results:
- WM damage in AD is not always regionally concordant with GM changes.
- DT MRI confirms severe WM involvement across AD variants and prodromal stages.
- Microstructural WM damage in AD is more extensive than predicted by cortical atrophy.
Conclusions:
- Alzheimer's disease significantly impacts white matter, supported by postmortem and in vivo data.
- WM damage may result from mechanisms beyond neuronal loss, like protein propagation or neuroinflammation.
- DT MRI provides valuable insights into AD pathophysiology and potential therapeutic targets.
