Frontal lobe dementia with novel tauopathy: Sporadic multiple system tauopathy with dementia

We present a novel tauopathy in a patient with a 10-yr history of progressi ve frontal lobe dementia and a negative family history. Autopsy revealed mi ld atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes. There were occasional filamentous tau-positive inclusions, but more interesting were numerous distinctive globular neuronal and glial tau-posi tive inclusions in both gray and white matter of the neocortex. Affected su bcortical regions included substantia nigra, globus pallidus, subthalamic n ucleus, and cerebellar dentate nucleus, in a distribution similar to progre ssive supranuclear palsy (PSP), but without significant accompanying neuron al loss or gliosis. Predominantly straight filaments were detected by elect ron microscopy (EM), while other inclusions were similar to fingerprint bod ies. No twisted ribbons were detected. Immuno-EM studies revealed that only the filamentous inclusions were composed of tau. Immunoblotting of sarkosy l-insoluble tau revealed 2 major bands of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed predominantly 4-repeat tau. Sequence analy sis of tau revealed that there were no mutations in either exons 9-13 or th e adjacent intronic sequences. The unique cortical tau pathology in this ca se of sporadic multiple system tauopathy with dementia adds a new pathologi c profile to the spectrum of tauopathies.