title: Pathological and Clinical Spectrum of Progressive Supranuclear Palsy: With Special Reference to Astrocytic Tau Pathology.
abstract: Progressive supranuclear palsy (PSP) is a four-repeat tauopathy with tau-positive, argyrophilic tuft-shaped astrocytes (TAs). We performed a pathological and clinical investigation in 40 consecutive autopsied Japanese patients with pathological diagnoses of PSP or PSP-like disease. Unequivocal TAs were present in 22 cases, all of which were confirmed to be PSP. Such TAs were hardly detected in the other 18 cases, which instead exhibited tau-positive, argyrophilic astrocytes, appearing as comparatively small clusters with central nuclei of irregularly shaped, coarse structures (equivocal TAs). Cluster analysis of the distribution pattern of tau-related pathology for these 18 cases identified two subgroups, pallido-nigro-luysian atrophy (PNLA) Type 1 (n = 9) and Type 2 (n = 9), the former being distinguished from the latter by the presence of tau-related lesions in the motor cortex, pontine nucleus and cerebellar dentate nucleus in addition to the severely affected PNL system. The duration from symptom onset until becoming wheelchair-bound was significantly longer in PNLA Type 1. Immunoblotting of samples from the three disease conditions revealed band patterns of low-molecular-mass tau fragments at ∼35 kDa. These findings shed further light on the wide pathological and clinical spectrum of four-repeat tauopathy, representing PSP in the broad sense rather than classical PSP.
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.|Department of Psychiatry, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiga
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Tada
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Department of Neurology, Sagamihara National Hospital, Sagamihara, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Molecular Neuroscience, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Onodera
authors.affiliation: Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ikeuchi
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000368:Aged; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D015151:Immunoblotting; D053208:Kaplan-Meier Estimate; D008297:Male; D016253:Microscopy, Immunoelectron; D012189:Retrospective Studies; D013494:Supranuclear Palsy, Progressive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins
keywords: glial tau pathology; pallido-nigro-luysian atrophy; progressive supranuclear palsy; tauopathy; tuft-shaped astrocyte