Studies on the practical diagnosis and pathomechanism of tauopathy as neurodegenerative disordrs

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1)Based on the analysis of the clinical, pathological and genetic features of the three families with tau N279K mutation, we have demonstrated that the clinical phenotype of N279K mutation was relatively uniform even in the families with unrelated founders. The pathologic changes involved the spinal cord as well as basal ganglia, and cerebral cortex and white matter.2)We have retrospectively reviewed 8 patients with autopsy-proven corticobasal degeneration and reported the variable clinical phenotypes including marked palilalia, progressive dysarthria, progressive dysphagia, and non-fluent aphasia.3)We transiently transfected mouse neuroblastoma cells (N18TG2) with wild-type tau or tau with the L266V mutation from a patient with familial frontotemporal dementia. Tau protein was observed in both the wild-type and L266V mutant tau transfectants, as were inclusions composed of tau phosphorylated at amino acids Thrl 81, Ser 202/Thr205, and Ser396. Inclusions immunoreactive with anti-tau antibodies AT8 and pS396 were also immunoreactive with antibodies against ubiquitin and glycogen synthase kinase 3□.4)We have revealed that progression of motor deterioration in the model mice with P301 tau mutation was inhibited by administration of lithium.