4R Tauopathies and Phenotypic Overlap: A Case Report

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Abstract
Four-repeat (4R) tauopathies, such as Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), often exhibit considerable phenotypic overlap, which complicates invivo diagnosis. This report presents a 62-year-old woman who initially presented clinical features of corticobasal syndrome, such as asymmetric parkinsonism, fixed right limb dystonia, and orobuccal apraxia. The later development of supranuclear vertical gaze palsy and recurrent falls led to a revised diagnosis of probable PSP. Neuropsychological evaluation identified a non-amnestic major neurocognitive disorder with severe executive dysfunction, attentional deficits, and apraxia. Neuroimaging contributed critical diagnostic information: FDG-PET revealed severe asymmetric cortical hypometabolism in the left frontoparietal regions, and MRI demonstrated marked midbrain atrophy with the hummingbird sign. Volumetric analysis further confirmed asymmetric cortical atrophy, predominantly in the left frontoparietal areas, as well as reduced brainstem volume. Negative genetic testing supported a sporadic etiology. This case underscores the complex clinical overlap within the 4R tauopathy spectrum, illustrating that PSP may present with a CBS phenotype. The findings support the clinical value of categorizing these disorders as probable 4R-tauopathies to facilitate early recognition. Integration of clinical, radiological, and volumetric data is crucial for diagnostic precision.