Voxel-Based Morphometry in Tau-Positive and Tau-Negative Frontotemporal Lobar Degenerations

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Abstract
Background: The identification of specific, diagnostically useful predictors of protein dysfunction in the frontotemporal lobar degenerations (FTLD) is a problem of great clinical and biological interest. Correlations between regional patterns of tissue loss and specific proteinopathies have not been established. Objective: Specific brain imaging correlates of protein tau dysfunction were sought using voxel-based morphometry in FTLD subgroups with and without tau pathology. Methods: Seventeen patients with pathologically or genetically confirmed diagnoses of FTLD who had undergone volumetric brain magnetic resonance imaging (MRI) were identified retrospectively and tau-positive (n = 9) and tau-negative (n = 8) subgroups were defined. MRI data were compared with healthy age- and sex-matched controls using voxel-based morphometry implemented in a statistical parametric mapping software package. Results: Compared with controls, tau-positive and tau-negative subgroups had extensive common areas of regional brain atrophy predominantly affecting the frontal and anterior temporal lobes. No specific brain imaging features were identified for either subgroup. Conclusion: Patterns of frontotemporal atrophy do not predict the presence or absence of tau pathology; conversely, different immunohistochemical profiles are associated with similar patterns of regional vulnerability to neuronal loss in FTLD.