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Updated: Jun 24, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
MRI correlates of protein deposition and disease severity in postmortem frontotemporal lobar degeneration
Jennifer L Whitwell1, Clifford R Jack, Matthew L Senjem
1Department of Radiology, Mayo Clinic Rochester, Rochester, Minn. 55905, USA.
Background:
Frontotemporal lobar degeneration (FTLD) can be classified based on the presence of the microtubule-associated protein tau and the TAR DNA binding protein-43 (TDP-43). Future treatments will likely target these proteins, therefore it is important to identify biomarkers to help predict protein biochemistry.
Objective:
To determine whether there is an MRI signature pattern of tau or TDP-43 using a large cohort of FTLD subjects and to investigate how patterns of atrophy change according to disease severity using a large autopsy-confirmed cohort of FTLD subjects.
Methods:
Patterns of gray matter loss were assessed using voxel-based morphometry in 37 tau-positive and 44 TDP-43-positive subjects compared to 35 age and gender-matched controls, and compared to each other. Comparisons were also repeated in behavioral variant frontotemporal dementia (bvFTD) subjects (n = 15 tau-positive and n = 30 TDP-43-positive). Patterns of atrophy were also assessed according to performance on the Clinical Dementia Rating (CDR) scale and Mini-Mental State Examination (MMSE).
Results:
The tau-positive and TDP-43-positive groups showed patterns of frontotemporal gray matter loss compared to controls with no differences observed between the groups, for all subjects and for bvFTD subjects. Patterns of gray matter loss increased in a graded manner by CDR and MMSE with loss in the frontal lobes, insula and hippocampus in mild subjects, spreading to the temporal and parietal cortices and striatum in more advanced disease.
Conclusion:
There is no signature pattern of atrophy for tau or TDP-43; however, patterns of atrophy in FTLD progress with measures of clinical disease severity.
Insights
No distinct MRI patterns differentiate tau or TDP-43 in frontotemporal lobar degeneration (FTLD). Instead, brain atrophy patterns worsen with disease severity, impacting various brain regions as FTLD progresses.
Area of Science:
- Neuroimaging
- Neuropathology
- Biomarker Discovery
Background:
- Frontotemporal lobar degeneration (FTLD) classification relies on tau or TAR DNA binding protein-43 (TDP-43) presence.
- Identifying biomarkers for protein biochemistry is crucial for developing targeted FTLD treatments.
Purpose of the Study:
- To identify potential MRI signature patterns associated with tau or TDP-43 in FTLD.
- To investigate how patterns of brain atrophy correlate with disease severity in FTLD.
Main Methods:
- Voxel-based morphometry analyzed gray matter loss in tau-positive and TDP-43-positive FTLD subjects versus controls.
- Comparisons were made between tau and TDP-43 groups, including in behavioral variant frontotemporal dementia (bvFTD).
- Atrophy patterns were assessed against Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) scores.
Main Results:
- Both tau-positive and TDP-43-positive groups exhibited frontotemporal gray matter loss compared to controls.
- No distinct MRI signature patterns were found to differentiate tau from TDP-43.
- Gray matter loss severity correlated with CDR and MMSE scores, with progression observed in mild to advanced disease stages.
Conclusions:
- There is no specific MRI atrophy pattern for tau or TDP-43 in FTLD.
- FTLD atrophy patterns demonstrably progress in correlation with clinical disease severity markers.
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