title: Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia.
abstract: Amyotrophic lateral sclerosis (ALS) may be accompanied by frontotemporal dementia (FTD). We report a case of glial mixed tau and TDP-43 proteinopathies in a Japanese patient diagnosed clinically as having ALS-D. Autopsy revealed loss of lower motor neurons and degeneration of the pyramidal tracts in the spinal cord and brain stem. The brain showed frontotemporal lobar degeneration (FTLD), the most severe neuronal loss and gliosis being evident in the precentral gyrus. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. AT8 immunostaining revealed that predominant occurrence of astrocytic tau lesions termed globular astrocytic inclusions (GAIs) was a feature of the affected regions. These GAIs were Gallyas-Braak negative. Neuronal and oligodendrocytic tau lesions were comparatively scarce. pS409/410 immunostaining also revealed similar neuronal and glial TDP-43 lesions. Interestingly, occasional co-localization of tau and TDP-43 was evident in the GAIs. Immunoblot analyses revealed band patterns characteristic of a 4-repeat (4R) tauopathy, corticobasal degeneration and a TDP-43 proteinopathy, ALS/FTLD-TDP Type B. No mutations were found in the MAPT or TDP-43 genes. We consider that this patient harbored a distinct, sporadic globular glial mixed 4R tau and TDP-43 proteinopathy associated with motor neuron disease and FTD.
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.|Department of Neurology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Ryoko
authors: R
authors: Takeuchi
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Yasuko
authors: Y
authors: Toyoshima
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Mari
authors: M
authors: Tada
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Hidetomo
authors: H
authors: Tanaka
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Hiroshi
authors: H
authors: Shimizu
authors: Department of Molecular Neuroscience, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Atsushi
authors: A
authors: Shiga
authors: Department of Neurology, Toyama Prefectural Central Hospital, Toyama, Japan.
authors: Takeshi
authors: T
authors: Miura
authors: Department of Neurology, Toyama Prefectural Central Hospital, Toyama, Japan.
authors: Kenju
authors: K
authors: Aoki
authors: Department of Pathology, Toyama Prefectural Central Hospital, Toyama, Japan.
authors: Akane
authors: A
authors: Aikawa
authors: Department of Pathology, Toyama Prefectural Central Hospital, Toyama, Japan.
authors: Shin
authors: S
authors: Ishizawa
authors: Department of Molecular Genetics, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Takeshi
authors: T
authors: Ikeuchi
authors: Department of Neurology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Masatoyo
authors: M
authors: Nishizawa
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Akiyoshi
authors: A
authors: Kakita
authors: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors: Hitoshi
authors: H
authors: Takahashi
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000473:pathology*; D006801:Humans; D016472:Motor Neuron Disease / Q000150:complications / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D014057:Tomography, X-Ray Computed; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D053327:Apolipoprotein E4; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000598624:TARDBP protein, human; D016875:tau Proteins
keywords: TDP-43; amyotrophic lateral sclerosis; astrocyte; frontotemporal lobar degeneration; motor neuron disease; tau