Four-repeat tauopathy clinically presenting as posterior cortical atrophy: atypical corticobasal degeneration?

A man aged 55 with negative family history presented with progressive decline in spatial orientation and visual functions for 2 years. He showed impaired optic fixation, optic ataxia, agraphia, acalculia, ideomotor apraxia, disturbed right-left differentiation but preserved color matching, memory and motor perception, gradually progressing to dementia, without extrapyramidal signs. Brain MRI and PET showed severe bilateral atrophy and hypometabolism in parieto-occipital areas with sparing of visual perception area and frontal lobes. Treatment with cholinesterase inhibitors had no effect. Death occurred 6A1/2 years after onset of symptoms from bronchopneumonia. Clinical diagnosis was posterior cortical atrophy (Benson's syndrome). Autopsy showed severe bilateral parietal cortical atrophy, less severe in other brain regions without subcortical lesions. Histology revealed severe diffuse tauopathy with neuronal loss, neurofibrillary tangles, neuropil threads, and tau deposits in astroglia and oligodendroglia in parietal, temporal, occipital cortex, less in frontal cortex and hippocampus, putamen, claustrum, thalamus and subthalamus. Severely involved white matter showed many tau-positive threads, comma-like inclusions in oligodendroglia (coiled bodies) and in astroglia. Mild neuronal loss in substantia nigra was associated with massive tau pathology, also involving several brainstem nuclei, cerebellum being preserved. There were neither astrocytic plaques nor any amyloid pathology. Neuronal and glial inclusions were generally 4R-tau-positive and 3R-tau-negative. No TDP-43 and alpha-synuclein inclusions were detected. Spinal cord was not available. No mutations were found in the MAPT gene. This is the first published case with the fully developed clinical and neuroimaging picture of posterior cortical atrophy, morphologically presenting as a distinct phenotype of 4R-tauopathy that closely resembles (atypical) CBD.