Publications by authors named "Hidetomo Tanaka"

8 Publications

  • Page 1 of 1

Structure-based classification of tauopathies.

Nature 2021 10 29;598(7880):359-363. Epub 2021 Sep 29.

MRC Laboratory of Molecular Biology, Cambridge, UK.

The ordered assembly of tau protein into filaments characterizes several neurodegenerative diseases, which are called tauopathies. It was previously reported that, by cryo-electron microscopy, the structures of tau filaments from Alzheimer's disease, Pick's disease, chronic traumatic encephalopathy and corticobasal degeneration are distinct. Here we show that the structures of tau filaments from progressive supranuclear palsy (PSP) define a new three-layered fold. Moreover, the structures of tau filaments from globular glial tauopathy are similar to those from PSP. The tau filament fold of argyrophilic grain disease (AGD) differs, instead resembling the four-layered fold of corticobasal degeneration. The AGD fold is also observed in ageing-related tau astrogliopathy. Tau protofilament structures from inherited cases of mutations at positions +3 or +16 in intron 10 of MAPT (the microtubule-associated protein tau gene) are also identical to those from AGD, suggesting that relative overproduction of four-repeat tau can give rise to the AGD fold. Finally, the structures of tau filaments from cases of familial British dementia and familial Danish dementia are the same as those from cases of Alzheimer's disease and primary age-related tauopathy. These findings suggest a hierarchical classification of tauopathies on the basis of their filament folds, which complements clinical diagnosis and neuropathology and also allows the identification of new entities-as we show for a case diagnosed as PSP, but with filament structures that are intermediate between those of globular glial tauopathy and PSP.
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http://dx.doi.org/10.1038/s41586-021-03911-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611841PMC
October 2021

Hemiplegic-type ALS: clinicopathological features of two autopsied patients.

J Neurol Neurosurg Psychiatry 2021 Sep 21;92(9):1014-1016. Epub 2021 Apr 21.

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

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http://dx.doi.org/10.1136/jnnp-2021-326257DOI Listing
September 2021

Comparison of Common and Disease-Specific Post-translational Modifications of Pathological Tau Associated With a Wide Range of Tauopathies.

Front Neurosci 2020 4;14:581936. Epub 2020 Nov 4.

Department of Brain and Neuroscience, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Tauopathies are the most common type of neurodegenerative proteinopathy, being characterized by cytoplasmic aggregates of hyperphosphorylated tau protein. The formation and morphologies of these tau inclusions, the distribution of the lesions and related metabolic changes in cytoplasm differ among different tauopathies. The aim of this study was to examine whether there are differences in the post-translational modifications (PTMs) in the pathological tau proteins. We analyzed sarkosyl-insoluble pathological tau proteins prepared from brains of patients with Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, globular glial tauopathy, and frontotemporal dementia and parkinsonisms linked to chromosome 17 with tau inclusions using liquid chromatography mass spectrometry. In pathological tau proteins associated with a wide range of tauopathies, 170 PTMs in total were identified including new PTMs. Among them, common PTMs were localized in the N- and C-terminal flanking regions of the microtubule binding repeats and PTMs, which were considered to be disease-specific, were found in microtubule binding repeats forming filament core. These suggested that the differences in PTMs reflected the differences in tau filament core structures in each disease.
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http://dx.doi.org/10.3389/fnins.2020.581936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672045PMC
November 2020

An autopsy case of peliosis hepatis with X-linked myotubular myopathy.

Leg Med (Tokyo) 2019 May 18;38:77-82. Epub 2019 Apr 18.

Division of Legal Medicine, Department of Community Preventive Medicine, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan; Center of Cause of Death Investigation, Faculty of Medicine, Niigata University, Niigata, Japan. Electronic address:

This report describes the autopsy case of a 4-year-old boy who died from hepatic hemorrhage and rupture caused by peliosis hepatis with X-linked myotubular myopathy. Peliosis hepatis is characterized by multiple blood-filled cavities of various sizes in the liver, which occurs in chronic wasting disease or with the use of specific drugs. X-linked myotubular myopathy is one of the most serious types of congenital myopathies, in which an affected male infant typically presents with severe hypotonia and respiratory distress immediately after birth. Although each disorder is rare, 12 cases of pediatric peliosis hepatis associated with X-linked myotubular myopathy have been reported, including our case. Peliosis hepatis should be considered as a cause of hepatic hemorrhage despite its low incidence, and it requires adequate gross and histological investigation for correct diagnosis.
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http://dx.doi.org/10.1016/j.legalmed.2019.04.005DOI Listing
May 2019

Globular glial tauopathy Type II: Clinicopathological study of two autopsy cases.

Neuropathology 2019 Apr 15;39(2):111-119. Epub 2019 Jan 15.

Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan.

Globular glial tauopathies (GGTs) are four-repeat tauopathies characterized by the presence of two types of tau-positive globular glial inclusions (GGIs): globular oligodendrocytic and astrocytic inclusions (GOIs and GAIs). GGTs are classified into three different neuropathological subtypes: Types I, II and III. We report two patients with GGTs - a 76-year-old woman and a 70-year-old man - in whom the disease duration was 5 and 6 years, respectively. Both patients exhibited upper and lower motor neuron signs and involuntary movements, and the latter also had dementia with frontotemporal cerebral atrophy evident on magnetic resonance imaging. Neuropathologically, in both cases, the precentral gyrus was most severely affected, and at the gray-white matter junction there was almost complete loss of Betz cells and occurrence of GOIs and coiled bodies with numerous neuropil threads. Both patients also showed neuronal loss and GGIs (mostly GOIs) in many other central nervous system regions, including the basal ganglia. Apart from the degree of regional severity, the distribution pattern was essentially the same in both cases. However, GAIs were not conspicuous in any of the affected regions. Based on the morphology and distribution pattern of the GGIs, we diagnosed the present two patients as having GGT Type II. Electron microscopic and biochemical findings in the former were consistent with the diagnosis. Type II cases are reported to be characterized by pyramidal features reflecting predominant motor cortex and corticospinal tract degeneration. The present observations suggest that a variety of neurological features, including dementia, can occur in GGT Type II reflecting widespread degeneration beyond the motor neuron system.
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http://dx.doi.org/10.1111/neup.12532DOI Listing
April 2019

Globular Glial Mixed Four Repeat Tau and TDP-43 Proteinopathy with Motor Neuron Disease and Frontotemporal Dementia.

Brain Pathol 2016 Jan 19;26(1):82-94. Epub 2015 May 19.

Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.

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.
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http://dx.doi.org/10.1111/bpa.12262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029069PMC
January 2016

[Case of cardiac tamponade during the treatment of acute cerebral infarction].

Rinsho Shinkeigaku 2014 ;54(3):218-22

Department of Neurology, Yamagata Prefectural Central Hospital.

A 59-year-old man was admitted to our hospital because of sudden weakness in his left foot. He had been treated for lung cancer by chemotherapy and irradiation 3 years earlier. Brain magnetic resonance (MR) imaging revealed multiple acute cerebral infarctions in the area of the right anterior cerebral artery. MR angiography (MRA) revealed that the right anterior cerebral artery was patent, with slight irregularity in the A3 portion. He was treated by administration of aspirin (200 mg/day) and a continuous intravenous unfragmented heparin infusion (10,000 IU/day). Four days after admission, he developed dyspnea. Chest computed tomography (CT) performed 5 days after admission revealed both a marked pericardial effusion and a pleural effusion. Emergency pericardiocentesis was therefore performed. While 1,000 ml of bloody pericardial effusion were aspirated, his dyspnea ameliorated dramatically. Histological examination of the pericardial effusion revealed infiltration of lung adenocarcinoma cells in the pericardium. Intracranial 3D-CT angiography revealed the pearl and string sign in the right anterior cerebral artery 6 days after admission. Anterior cerebral artery dissection was diagnosed as the cause of his cerebral infarction. It is important to recognize the possibility of cardiac tamponade as an uncommon complication of the treatment for acute cerebral infarction.
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http://dx.doi.org/10.5692/clinicalneurol.54.218DOI Listing
April 2015

An elderly Japanese patient with adult-onset type II citrullinemia with a novel D493G mutation in the SLC25A13 gene.

Intern Med 2012 15;51(16):2131-4. Epub 2012 Aug 15.

Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Faculty of Medicine, Yamagata University, Japan.

Mutations in the SLC25A13 gene lead to neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia (CTLN2). A 62-year-old man presented with recurrent episodes of neuropsychiatric manifestations. On admission, he had disorientation and flapping tremor. Laboratory data showed hyperferritinemia in addition to postprandial hyperammonemia and citrullinemia. A liver biopsy specimen revealed moderate hemosiderin deposits and hepatocytes with macrovesicular fat droplets. Genetic analysis of the SLC25A13 gene identified the previously reported p.S225X mutation and a novel p.D493G mutation. Hyperferritinemia might also be a characteristic finding of CTLN2-related fatty changes of the liver.
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http://dx.doi.org/10.2169/internalmedicine.51.7644DOI Listing
November 2012
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