Alzheimer's Imaging Consortium

Area of Science:

• Neuroscience
• Neuropathology
• Radiology

Background:

• Frontotemporal dementia (FTD) presents with similar clinical syndromes despite distinct proteinopathies (tau vs. TDP-43).
• Previous research indicated tau pathology in lower cortical layers and TDP-43 in upper layers.
• Investigating the impact of pathology distribution on cortical architecture is crucial.

Purpose of the Study:

• To assess the utility of cortical diffusivity metrics in distinguishing FTLD subtypes.
• To explore the relationship between laminar pathology distribution and cortical microstructural changes.

Main Methods:

• Structural and diffusion MRI (dMRI) were used to calculate cortical diffusivity (PerpPD+) in 40 autopsy-confirmed FTD cases (20 FTLD-tau, 20 FTLD-TDP).
• Ratios of layer pathology (RLP) were generated for a subgroup of 17 cases.
• Statistical analyses included linear models and partial Spearman's rank correlation, controlling for relevant covariates.

Main Results:

• Higher PerpPD+ values were observed in FTLD-tau cases, particularly in fronto-temporal regions.
• Significant differences in PerpPD+ were found in paralimbic and association macroregions.
• Correlations between PerpPD+ and RLP values were identified in specific cortical regions.

Conclusions:

• PerpPD+ effectively distinguishes cortical microstructural alterations in FTLD-tau versus FTLD-TDP.
• The correlation between PerpPD+ and laminar pathology ratios confirms PerpPD+ as a sensitive MRI marker for tau pathology distribution.