110 results on '"Takatama M"'
Search Results
2. Ultrastructure of diffuse plaques in senile dementia of the Alzheimer type: comparison with primitive plaques
- Author
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Yamaguchi, H., Nakazato, Y., Shoji, M., Takatama, M., and Hirai, S.
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- 1991
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Catalog
3. Light and electron microscopic and immunohistochemical observations of the Onuf's nucleus of amyotrophic lateral sclerosis
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Okamoto, K., Hirai, S., Ishiguro, K., Kawarabayashi, T., and Takatama, M.
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- 1991
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4. Different roles of arteriosclerosis in the rupture of intracranial dissecting aneurysms
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Sakata, N, Takebayashi, S, Kojima, M, Masawa, N, Suzuki, K, Takatama, M, Kusumi, Y, and Mitsumata, M
- Published
- 2001
5. FP07-MO-05 Neuropathological studies of patients with non-herpetic acute limbic encephalitis
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Okamoto, K., primary, Yoshida, M., additional, Banno, H., additional, Mochizuki, Y., additional, Nishiguchi, A., additional, Hamano, T., additional, Nishimura, M., additional, and Takatama, M., additional more...
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- 2009
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6. Pathology of a dissecting intracranial aneurysm.
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Sakata, N., Takebayashi, S., Kojima, M., Masawa, N., Suzuki, K., and Takatama, M.
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INTRACRANIAL aneurysms ,HISTOPATHOLOGY - Abstract
The pathological findings of six autopsy cases of dissecting intracranial aneurysm are studied. Clinically, all cases exhibited systemic hypertension or left ventricular hypertrophy. Macroscopically, all cases exhibited rupture of the vertebral artery and subarachnoid hemorrhage. Two types of lesion were present. First, all cases showed the formation of a dilatated pseudoaneurysm with widespread disruption of the entire arterial wall, which was composed of thin adventitia. Second, a medial disruption of the arterial wall and subadventitial dissecting hemorrhage, which formed a false lumen and stenosis of the ‘true’ lumen of the artery, was also found. However, these lesions were found to be connected to the site of rupture. The autopsy cases within 1 day of onset of intracranial dissecting aneurysm showed the formation of fibrin thrombus, a marked degree of leukocyte infiltration and necrosis of the arterial wall at the site of the lesion. The cases that survived more than 1 week showed smooth muscle cell proliferation, macrophage accumulation and lymphocytic infiltration. No arteriosclerosis was found in any lesion studied. These data suggest that the disruption of the entire arterial wall might initially occur and cause medial disruption and subadventitial hemorrhage. Hypertension and arteriosclerosis might function as causal and protective factors in the pathogenesis of dissecting intracranial aneurysms, respectively. [ABSTRACT FROM AUTHOR] more...
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- 2000
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7. The involvement of the neuronal Golgi apparatus and trans-Golgi network in the human olivary hypertrophy
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Takamine, K., Okamoto, K., Fujita, Y., Sakurai, A., Takatama, M., and Gonatas, N. K.
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- 2000
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8. IMMUNOGOLD ELECTRON MICROSCOPIC STUDY OF CEREBROVASCULAR AND SENILE PLAQUE AMYLOID BY USE OF ANTI-?? PROTEIN ANTIBODY
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OKAMOTO, K., primary, YAMAGUCHI, H., additional, HIRAI, S., additional, SHOJI, M., additional, HARIGAYA, Y., additional, and TAKATAMA, M., additional
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- 1988
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9. A STUDY OF ?? PROTEIN PRECURSOR BY USING ANT I SERUM AGAINST A SYNTHETIC PEPTIDE(1???28)
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HARIGAYA, Y., primary, SHOJI, M., additional, YAMAGUCHI, H., additional, HIRAI, S., additional, and TAKATAMA, M., additional
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- 1988
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10. IMMUNOCYTOCHEMICAL STUDY FOR ?? 1-ANTICHYMOTRYPSIN IN THE SENESCENT CEREBRAL AMYLOID
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SHOJI, M., primary, HARIGAYA, Y., additional, YAMAGUCHI, H., additional, OKAMOTO, K., additional, HIRAI, S., additional, and TAKATAMA, M., additional
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- 1988
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11. A case of the iatrogenic transmission of vascular Aß40 amyloid.
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Kawarabayashi T, Nakamura T, Takatama S, Miyamoto N, Iwai T, Naito I, Sugawara T, Ishizawa K, Hashimoto K, Amari M, Ikeuchi T, Kasahara H, Ikeda Y, Takatama M, and Shoji M
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- 2024
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12. High levels of plasma neurofilament light chain correlated with brainstem and peripheral nerve damage.
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Nakamura T, Kawarabayashi T, Shibata M, Kasahara H, Makioka K, Sugawara T, Oka H, Ishizawa K, Amari M, Ueda T, Kinoshita S, Miyamoto Y, Kaito K, Takatama M, Ikeda Y, and Shoji M
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Adult, Biomarkers blood, Peripheral Nerves pathology, Cohort Studies, ROC Curve, Neurofilament Proteins blood, Brain Stem diagnostic imaging, Brain Stem pathology
- Abstract
Background and Objectives: Blood neurofilament light chain (NfL) is a minimally invasive, but highly sensitive biomarker of neurological diseases. However, diseases and neurological damage associated with increased NfL remain unclear. Therefore, the present study investigated factors associated with increased plasma NfL levels in various neurological diseases, focal lesions and pathological processes., Methods: This was a retrospective cohort study on 410 participants with various neurological diseases and 17 healthy and cognitively unimpaired controls (HCU). Plasma samples were analyzed to measure NfL using ECL immunoassay. The focal lesions were classified as the cerebrum, cerebellum, brainstem, meninges, spinal cord, peripheral nerves, neuromuscular junction, and muscles based on medical records. A multiple regression analysis and receiver operating characteristic curve (ROC) analysis were performed to investigate whether plasma NfL levels predict specific diseases and focal lesions., Results: Plasma NfL levels discriminated between the HCU and all disease groups (area under the curve (AUC), 0.97), with a cut-off value of 63.4 pg/mL. A multiple regression analysis of focal lesions adjusted by pathogenic processes showed that brainstem and peripheral nerve involvement was associated with higher plasma NfL levels. A cut-off value of 53.8 pg/mL of NfL discriminated between the HCU and neurological disease group except for brainstem or peripheral disorders (AUC 0.962), while a cut-off value of 208.0 pg/mL distinguished this group from brainstem or peripheral nervous system disorders (AUC 0.716)., Discussion: These results demonstrate that plasma NfL has a potential to be a highly sensitive biomarker for neurological diseases and focal lesions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...
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- 2024
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13. A case of chronic progressive autoimmune GFAP astrocytopathy with extensive meningoencephalomyelitis and contrast enhancement on MRI.
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Oka H, Nakamura T, Sugawara T, Ishizawa K, Amari M, Kawarabayashi T, Okamoto K, Takatama M, Nakata S, Yoshimoto Y, Yamazaki A, Yokoo H, Kimura A, Shimohata T, Ikeda Y, and Shoji M
- Abstract
•We herein present a case of chronic progressive autoimmune GFAP astrocytopathy.•Symmetrical high-intensity signals on FLAIR were observed in the white matter of the temporal and occipital lobes, lateral cerebral ventricle walls, hippocampus, amygdala, and occipital cortex, with extensive Gd enhancement in radial perivascular lesions and the ependyma in the choroid plexus.•Improvements were achieved by 4 courses of IVMP and one of IVIg., Competing Interests: None., (© 2024 The Authors.) more...
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- 2024
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14. Role of complement activation and disruption of the blood-brain barrier in the pathogenesis of multiple system atrophy.
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Shibata M, Makioka K, Nakamura T, Kasahara H, Yamazaki T, Takatama M, Okamoto K, and Ikeda Y
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- Humans, Blood-Brain Barrier metabolism, alpha-Synuclein metabolism, Brain metabolism, Microglia metabolism, Complement Activation, Multiple System Atrophy pathology
- Abstract
Multiple system atrophy (MSA) is a progressive and sporadic neurodegenerative disorder characterized by the histological appearance of glial cytoplasmic inclusions primarily composed of α-synuclein. Recently, complement-mediated neuroinflammation has been proposed as a key factor in the pathogenesis of numerous neurodegenerative disorders. We conducted immunohistochemical/immunofluorescent assays targeting a number of complements to explore the role of complements in MSA pathogenesis using brain samples from deceased patients and controls. Complement deposition was notably increased in the cerebral vasculature and myelin sheath in the MSA brains. Furthermore, fibrinogen leakage resulting from the disruption of the blood-brain barrier (BBB) was observed, along with the presence of C1q-positive microglia clusters surrounding the MSA brain vessels. These immunohistochemical/immunofluorescent findings suggest that complement activation and BBB disruption play critical roles in MSA progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...
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- 2024
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15. Annual stability of the plasma Aß40/42 ratio and associated factors.
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Nakamura T, Kawarabayashi T, Nakahata N, Itoh K, Ihara K, Nakaji S, Ikeda Y, Takatama M, and Shoji M
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- Aged, Middle Aged, Humans, Young Adult, Adult, Aged, 80 and over, Aging, Brain, Heterozygote, Biomarkers, Apolipoproteins E, Alzheimer Disease
- Abstract
Objective: The plasma Aß40/42 ratio is a biomarker of brain amyloidosis. However, the threshold difference between amyloid positivity and negativity is only 10-20% and fluctuates with circadian rhythms, aging, and APOE-ε4 during the decades of evolution of Alzheimer's disease., Methods: Plasma Aß40 and Aß42 levels in 1472 participants aged between 19 and 93 years in the Iwaki Health Promotion Project for 4 years were statistically analyzed., Results: The means and standard deviations of annual inter-individual coefficients of variation were 5.3 ± 3.2% for Aß40, 7.8 ± 4.6% for Aß42, and 6.4 ± 4.1% for the Aß40/42 ratio. No significant age-dependent changes were observed in inter-individual coefficients of variation. Age-dependent increases in Aβ42 levels were suppressed, whereas those in the Aβ40/42 ratio were enhanced in APOE-ε4 carriers. The change points of Aß42, Aß40, and the Aß40/42 ratio were 36.4, 38.2, and 43.5 years, respectively. In the presence of APOE-ε4, the Aß40/42 ratio increased in middle-aged and elderly subjects while Aβ42 levels decreased in elderly subjects., Interpretation: Individual values for Aß40, Aß42, and the Aß40/42 ratio did not fluctuate annually or in an age-dependent manner. If the plasma Aβ40/42 ratio changes by more than 14.7% (+2 standard deviations) relative to age- and APOE-ε4-adjusted normal annual fluctuations, other biomarkers also need to be examined., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.) more...
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- 2023
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16. Plasma ApoE4 Levels Are Lower than ApoE2 and ApoE3 Levels, and Not Associated with Plasma Aβ40/42 Ratio as a Biomarker of Amyloid-β Amyloidosis in Alzheimer's Disease.
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Nakamura T, Kawarabayashi T, Ueda T, Shimomura S, Hoshino M, Itoh K, Ihara K, Nakaji S, Takatama M, Ikeda Y, and Shoji M
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- Female, Humans, Male, Apolipoprotein E2 genetics, Apolipoprotein E4 metabolism, Apolipoprotein E3, Chromatography, Liquid, Tandem Mass Spectrometry, Apolipoproteins E genetics, Apolipoproteins E metabolism, Cholesterol, Biomarkers, Protein Isoforms, Alzheimer Disease diagnosis, Alzheimer Disease genetics, Alzheimer Disease metabolism, Amyloidosis
- Abstract
Background: APOE4 is the strongest risk factor for Alzheimer's disease (AD). However, limited information is currently available on APOE4 and the pathological role of plasma apolipoprotein E (ApoE) 4 remains unclear., Objective: The aims of the present study were to measure plasma levels of total ApoE (tE), ApoE2, ApoE3, and ApoE4 using mass spectrometry and elucidate the relationships between plasma ApoE and blood test items., Methods: We herein examined plasma levels of tE, ApoE2, ApoE3, and ApoE4 in 498 subjects using liquid chromatograph-mass spectrometry (LC-MS/MS)., Results: Among 498 subjects, mean age was 60 years and 309 were female. tE levels were distributed as ApoE2/E3 = ApoE2/E4 >ApoE3/E3 = ApoE3/E4 >ApoE4/E4. In the heterozygous group, ApoE isoform levels were distributed as ApoE2 >ApoE3 >ApoE4. ApoE levels were not associated with aging, the plasma amyloid-β (Aβ) 40/42 ratio, or the clinical diagnosis of AD. Total cholesterol levels correlated with the level of each ApoE isoform. ApoE2 levels were associated with renal function, ApoE3 levels with low-density lipoprotein cholesterol and liver function, and ApoE4 levels with triglycerides, high-density lipoprotein cholesterol, body weight, erythropoiesis, and insulin metabolism., Conclusion: The present results suggest the potential of LC-MS/MS for the phenotyping and quantitation of plasma ApoE. Plasma ApoE levels are regulated in the order of ApoE2 >ApoE3 >ApoE4 and are associated with lipids and multiple metabolic pathways, but not directly with aging or AD biomarkers. The present results provide insights into the multiple pathways by which peripheral ApoE4 influences the progression of AD and atherosclerosis. more...
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- 2023
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17. Clinical Evaluation of Cerebrospinal Fluid p217tau and Neurofilament Light Chain Levels in Patients with Alzheimer's Disease or Other Neurological Diseases.
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Kawarabayashi T, Nakamura T, Miyashita K, Segawa T, Fukamachi I, Sugawara T, Oka H, Ishizawa K, Amari M, Kasahara H, Makioka K, Ikeda Y, Takatama M, and Shoji M
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- Humans, Amyloid beta-Peptides cerebrospinal fluid, Biomarkers cerebrospinal fluid, Intermediate Filaments, Neurofilament Proteins cerebrospinal fluid, tau Proteins cerebrospinal fluid, Alzheimer Disease diagnosis, Alzheimer Disease cerebrospinal fluid
- Abstract
Background: The cerebrospinal fluid (CSF) levels of tau phosphorylated at threonine 217 (p217tau) or 181 (p181tau), and neurofilament light chain (NfL) are definite biomarkers of tauopathy and neurodegeneration in Alzheimer's disease (AD)., Objective: To validate their utility in excluding other neurological diseases and age-related changes in clinical settings., Methods: We developed monoclonal antibodies against p217tau and NfL, established novel ELISAs, and analyzed 170 CSF samples from patients with AD or other neurological diseases., Results: In AD, p217tau is a more specific and abundant CSF component than p181tau. However, CSF NfL levels increase age-dependently and to a greater extent in central and peripheral nervous diseases than in AD., Conclusions: CSF p217tau correlates better with AD neurodegeneration than other tau-related biomarkers and the major phosphorylated tau species. The clinical usage of NfL as a neurodegeneration biomarker in AD requires exclusion of various central and peripheral neurological diseases. more...
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- 2023
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18. A comparison of cerebral amyloid angiopathy in the cerebellum and CAA-positive occipital lobe of 60 brains from routine autopsies.
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Okamoto K, Amari M, Ikeda M, Fukuda T, Suzuki K, and Takatama M
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- Humans, Amyloid beta-Peptides metabolism, Plaque, Amyloid pathology, Brain pathology, Occipital Lobe pathology, Alzheimer Disease pathology, Cerebral Amyloid Angiopathy pathology
- Abstract
We semiquantitatively compared the frequency and severity of cerebral amyloid angiopathy (CAA) in the cerebellum and CAA-positive occipital lobe of 60 subjects from routine autopsies. In the 60 subjects with a CAA-positive occipital lobe, cerebellar CAA was observed in 29 subjects (48.3%), and the severity of cerebellar CAA was relatively mild compared with occipital lobe CAA. Capillary CAA was observed in the occipital lobe of 12 subjects and the cerebellum of three subjects. CAA-related vasculopathies were observed in the occipital lobe of 15 subjects and the cerebellum of two subjects. The severity of CAA-related vasculopathy was mild in both of these subjects. Amyloid-β plaques were observed in the occipital lobe of 54 subjects (90%) and the cerebellum of 16 subjects (26.7%). The severity of amyloid-β plaques in the cerebellum was mild compared with the occipital lobe. In summary, we confirmed that cerebellar CAA is frequently observed in the cerebellum but with a lower severity than CAA in the occipital lobe., (© 2022 Japanese Society of Neuropathology.) more...
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- 2022
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19. An autopsy case of amyloid angiopathy-related cerebellar hemorrhage.
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Okamoto K, Amari M, Iwai T, Fukuda T, Suzuki K, and Takatama M
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- Aged, 80 and over, Amyloid beta-Peptides, Autopsy, Cerebral Hemorrhage complications, Humans, Male, Plaque, Amyloid, Alzheimer Disease, Cerebral Amyloid Angiopathy complications
- Abstract
An 80-year-old man with dementia demonstrated cerebellar hemorrhage. Autopsy revealed pathology compatible with Alzheimer's disease and cerebral amyloid angiopathy (CAA). CAA was more prevalent in the occipital lobe than in the frontal, parietal, and temporal lobes; however, amyloid-β (Aβ)-containing senile plaques were less abundant in the occipital cortex than in the other cortices. In the cerebellum, abundant CAA-involved vessels were observed in the subarachnoid space and molecular layer and to a lesser extent in the Purkinje and granule layers. On consecutive sections, Aβ
1-42 immunohistochemistry revealed senile plaques and CAA-involved vessels with strong immunoreactivity whereas Aβ1-40 immunohistochemistry identfied CAA-involved vessels with strong immunoreactivity and senile plaques with weak immunoreactivity in the cerebellar cortices., (© 2022 Japanese Society of Neuropathology.) more...- Published
- 2022
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20. Polygenic variants related to familial hypobetalipoproteinemia in a patient with Alzheimer's disease homozygotic for the APOE ε2 allele presenting multiple cortical superficial siderosis and recurrent lobar hemorrhages.
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Ikeda M, Okamoto K, Suzuki K, Amari M, Takai E, Takatama M, Yokoo H, Ishibashi S, and Ikeda Y
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- Alleles, Apolipoprotein E2 genetics, Hemorrhage, Humans, Alzheimer Disease complications, Alzheimer Disease genetics, Hypobetalipoproteinemias, Siderosis
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- 2022
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21. Lipid Rafts Act as a Common Platform for Amyloid-β Oligomer-Induced Alzheimer's Disease Pathology.
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Kawarabayashi T, Nakamura T, Sato K, Seino Y, Ichii S, Nakahata N, Takatama M, Westaway D, George-Hyslop PS, and Shoji M
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- Animals, Disease Models, Animal, Mice, Mice, Transgenic, Phosphorylation, Prion Proteins analysis, Prion Proteins metabolism, tau Proteins metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, Amyloid beta-Peptides analysis, Amyloid beta-Peptides metabolism, Membrane Microdomains metabolism, Membrane Microdomains pathology
- Abstract
Background: Amyloid-β (Aβ) oligomers induce the overproduction of phosphorylated tau and neurodegeneration. These cascades gradually cause cognitive impairment in Alzheimer's disease (AD). While each pathological event in AD has been studied in detail separately, the spatial and temporal relationships between pathological events in AD remain unclear., Objective: We demonstrated that lipid rafts function as a common platform for the pathological cascades of AD., Methods: Cellular and synaptosomal lipid rafts were prepared from the brains of Aβ amyloid model mice (Tg2576 mice) and double transgenic mice (Tg2576 x TgTauP301L mice) and longitudinally analyzed., Results: Aβ dimers, the cellular prion protein (PrPc), and Aβ dimer/PrPc complexes were detected in the lipid rafts. The levels of Fyn, the phosphorylated NR2B subunit of the N-methyl-D-aspartate receptor, glycogen synthase kinase 3β, total tau, phosphorylated tau, and tau oligomers increased with Aβ dimer accumulation in both the cellular and synaptosomal lipid rafts. Increases in the levels of these molecules were first seen at 6 months of age and corresponded with the early stages of Aβ accumulation in the amyloid model mice., Conclusion: Lipid rafts act as a common platform for the progression of AD pathology. The findings of this study suggest a novel therapeutic approach to AD, involving the modification of lipid raft components and the inhibition of their roles in the sequential pathological events of AD. more...
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- 2022
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22. IgG4-related hypothalamo-hypophysitis.
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Urushida Y, Ishikawa D, Yanaizumi M, Nakamura T, Amari M, Kawarabayashi T, Tosaka M, Ikeda Y, Takatama M, and Shoji M
- Abstract
•A patient exhibited IgG4-related hypothalamo-hypophysitis.•Prominent high-signal areas of swelling were observed in the hypothalamus, tuber cinereum, infundibulum, and bilateral optic nerve systems.•MRI T1WI with contrast media demonstrated enhanced neurohypophysis and cystic swelling, and compressed anterior pituitary.•MRI findings improved rapidly after 4 days of steroid therapy., (© 2021 The Authors.) more...
- Published
- 2021
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23. Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18 F-THK5351 Positron Emission Tomography: A Case Report.
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Ikeda M, Okamoto K, Suzuki K, Takai E, Kasahara H, Furuta N, Furuta M, Tashiro Y, Shimizu C, Takatama S, Naito I, Sato M, Sakai Y, Takahashi M, Amari M, Takatama M, Higuchi T, Tsushima Y, Yokoo H, Kurabayashi M, Ishibashi S, Ishii K, and Ikeda Y more...
- Abstract
In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the
11 C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease.18 F-THK5351 PET revealed that the accumulation of18 F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover,18 F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B).18 F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides,18 F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The18 F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ikeda, Okamoto, Suzuki, Takai, Kasahara, Furuta, Furuta, Tashiro, Shimizu, Takatama, Naito, Sato, Sakai, Takahashi, Amari, Takatama, Higuchi, Tsushima, Yokoo, Kurabayashi, Ishibashi, Ishii and Ikeda.) more...- Published
- 2021
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24. Improved Neuroimaging Findings and Cognitive Function in a Case of High-altitude Cerebral Edema.
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Urushida Y, Kikuchi Y, Shimizu C, Amari M, Kawarabayashi T, Nakamura T, Ikeda Y, Takatama M, and Shoji M
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- Altitude, Cognition, Humans, Neuroimaging, Altitude Sickness complications, Altitude Sickness diagnostic imaging, Brain Edema diagnostic imaging, Brain Edema etiology
- Abstract
High-altitude cerebral edema (HACE) is a rare condition of acute mountain sickness that manifests as consciousness disturbance and truncal ataxia. Neuroimaging shows vasogenic edema with microbleeds in the white matter and the corpus callosum. We herein report a case of HACE in which the patient showed widespread hyperintense signals with extensive microbleeds in the white matter and corpus callosum on MRI, as well as cognitive dysfunction. Rehabilitation to improve the higher brain function facilitated the recovery of the patient's cognitive impairment and was accompanied by improved MRI findings. more...
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- 2021
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25. Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.
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Ikeda M, Kodaira S, Kasahara H, Takai E, Nagashima K, Fujita Y, Makioka K, Hirayanagi K, Furuta N, Furuta M, Sanada E, Kobayashi A, Harigaya Y, Nagamine S, Hattori N, Tashiro Y, Kishi K, Shimada H, Suto T, Tanaka H, Sakai Y, Yamazaki T, Tanaka Y, Aihara Y, Amari M, Yamaguchi H, Okamoto K, Takatama M, Ishii K, Higuchi T, Tsushima Y, and Ikeda Y more...
- Abstract
Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by
99m Tc-ethyl cysteinate dimer single photon emission computerized tomography (99m Tc ECD-SPECT), as well as the mean cortical standard uptake value ratio by11 C-labeled Pittsburgh Compound B-positron emission tomography (11 C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ikeda, Kodaira, Kasahara, Takai, Nagashima, Fujita, Makioka, Hirayanagi, Furuta, Furuta, Sanada, Kobayashi, Harigaya, Nagamine, Hattori, Tashiro, Kishi, Shimada, Suto, Tanaka, Sakai, Yamazaki, Tanaka, Aihara, Amari, Yamaguchi, Okamoto, Takatama, Ishii, Higuchi, Tsushima and Ikeda.) more...- Published
- 2021
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26. Age-Related Cognitive Decline and Prevalence of Mild Cognitive Impairment in the Iwaki Health Promotion Project.
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Nakahata N, Nakamura T, Kawarabayashi T, Seino Y, Ichii S, Ikeda Y, Amari M, Takatama M, Murashita K, Ihara K, Itoh K, Nakaji S, and Shoji M
- Subjects
- Aged, Aging physiology, Alzheimer Disease genetics, Cohort Studies, Female, Humans, Japan, Magnetic Resonance Imaging, Male, Middle Aged, Prevalence, Quality of Life psychology, Cognitive Dysfunction diagnosis, Health Promotion, Mental Status and Dementia Tests statistics & numerical data, Neuropsychological Tests statistics & numerical data
- Abstract
Background: The Iwaki Health Promotion Project (IHPP) is a community-based study for the prevention of lifestyle-related diseases and improvement of quality of life., Objective: Between 2014 and 2017, a total of 4,442 Iwaki town residents from 19 to 93 years of age participated in annual surveys to clarify the natural course of age-related cognitive decline and mild cognitive impairment (MCI)., Methods: Modified OLD and SED-11Q questionnaires, MMSE, Logical Memory II, educational history, and APOE genotypes were examined at the first screening. MCI and dementia were diagnosed at the second examination by detailed neurological examination, CDR, and MRI, and followed for 3 years. Spline regression analyses based on a linear mixed model was adopted for statistical analysis., Results: MMSE scores declined with age from 55 to 64 years. There was also interaction between levels of education and ages. At the second examination, 56 MCI and 5 dementia patients were identified. None of the MCI cases progressed to dementia during the 3 years. During follow-up examinations, 13 cases showed improved MMSE scores (0.95 point/year), 5 remained stable, and 7 deteriorated (-0.83 point/year). Five cases showed improved CDR-SOB scores (-0.28 point/year), 9 remained stable, and 6 deteriorated (0.3 point/year)., Conclusion: IHPP revealed that age- and education-related cognitive decline began and advanced from 55 years of age. The prevalence of MCI and dementia was estimated to be 5.9%in the Iwaki town cohort over 60 yeas of age. About 30%of MCI cases showed progression of cognitive decline. more...
- Published
- 2021
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27. Quantitative Measurement of Cerebrospinal Fluid Amyloid-β Species by Mass Spectrometry.
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Seino Y, Nakamura T, Harada T, Nakahata N, Kawarabayashi T, Ueda T, Takatama M, and Shoji M
- Subjects
- Humans, Amyloid beta-Peptides cerebrospinal fluid, Biomarkers cerebrospinal fluid, Chromatography, High Pressure Liquid, Tandem Mass Spectrometry
- Abstract
Background: High sensitivity liquid chromatography mass spectrometry (LC-MS/MS) was recently introduced to measure amyloid-β (Aβ) species, allowing for a simultaneous assay that is superior to ELISA, which requires more assay steps with multiple antibodies., Objective: We validated the Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 assay by LC-MS/MS and compared it with ELISA using cerebrospinal fluid (CSF) samples to investigate its feasibility for clinical application., Methods: CSF samples from 120 subjects [8 Alzheimer's disease (AD) with dementia (ADD), 2 mild cognitive dementia due to Alzheimer's disease (ADMCI), 14 cognitively unimpaired (CU), and 96 neurological disease subjects] were analyzed. Aβ species were separated using the Shimadzu Nexera X2 system and quantitated using a Qtrap 5500 LC-MS/MS system. Aβ1-40 and Aβ1-42 levels were validated using ELISA., Results: CSF levels in CU were 666±249 pmol/L in Aβ1-38, 2199±725 pmol/L in Aβ1-40, 153.7±79.7 pmol/L in Aβ1-42, and 9.78±4.58 pmol/L in Aβ1-43. The ratio of the amounts of Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-43 was approximately 68:225:16:1. Linear regression analyses showed correlations among the respective Aβ species. Both Aβ1-40 and Aβ1-42 values were strongly correlated with ELISA measurements. No significant differences were observed in Aβ1-38 or Aβ1-40 levels between AD and CU. Aβ1-42 and Aβ1-43 levels were significantly lower, whereas the Aβ1-38/1-42, Aβ1-38/1-43, and Aβ1-40/Aβ1-43 ratios were significantly higher in AD than in CU. The basic assay profiles of the respective Aβ species were adequate for clinical usage., Conclusion: A quantitative LC-MS/MS assay of CSF Aβ species is as reliable as specific ELISA for clinical evaluation of CSF biomarkers for AD. more...
- Published
- 2021
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28. Successful basilar artery dilatation in pure bilateral cerebral peduncular infarctions using balloon angioplasty.
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Kikuchi Y, Miyamoto N, Urushida Y, Shimizu C, Amari M, Kawarabayashi T, Nakamura T, Takatama S, Naito I, Ikeda Y, Takatama M, and Shoji M
- Abstract
•An extremely rare case of bilateral cerebral peduncular infarctions (BCPI) is reported.•The detection of the pure Mickey Mouse ears sign on MRI is an indicator of a need for reperfusion therapy.•Severe stenosis of the basilar artery (BA) and a poor collateral supply from both posterior cerebral arteries were seen.•Balloon angioplasty for the BA stenosis ameliorated the stenosis and produced a favorable outcome., Competing Interests: None., (© 2020 The Author(s).) more...
- Published
- 2020
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29. Amyloid-β plaques may be reduced in advanced stages of cerebral amyloid angiopathy in the elderly.
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Okamoto K, Amari M, Fukuda T, Suzuki K, and Takatama M
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Occipital Lobe pathology, Brain pathology, Cerebral Amyloid Angiopathy pathology, Plaque, Amyloid pathology
- Abstract
We examined 29 cases in which cerebral amyloid angiopathy (CAA) was detected among routine aged autopsies. Most cases with severe CAA had many amyloid-β (Aβ) plaques in the occipital cortex. Nonetheless, two cases had few Aβ plaques with many small vessels and capillaries with CAA. In the two cases, severe CAA was widely distributed, except in the frontal lobes. Aβ deposits in capillaries often showed the characteristic pattern of dysphoric amyloid angiopathy. A few naked plaques were present. Although Aβ plaques were sparse near small vessels with CAA, there were many Aβ plaques distant from small vessels with CAA. Some of the remaining plaques had a moth-eaten appearance. Based on Aβ-positive star-like appearance and results of double immunohistochemistry for glial fibrillary acidic protein and Aβ
1-42 , some astrocytes appeared to contain Aβ. Ionized calcium-binding adapter molecule 1 (Iba1)-positive microglia were scattered within the neuropil, with some present around small vessels with CAA. Iba1-positive microglia also seemed to phagocytose Aβ in several senile plaques by double immunostaining. Neurons and neurites identified with a monoclonal antibody against phosphorylated tau (clone AT8) were occasionally detected in sparse plaque areas, with AT8-identified dot-like structures present around capillaries with CAA. Accumulation of T lymphocytes was detected around vessels in the subarachnoid space in one case. The morphological changes detected in our two cases were similar to those of morphological markers of plaque clearance after Aβ immunotherapy. Nonetheless, our cases did not receive Aβ immunotherapy, but similar pathologies were observed. Overall, advanced CAA cases, including our two cases, may be examples of plaque clearance without Aβ immunotherapy. Further studies are needed to resolve the mechanism of Aβ plaque clearance using these cases., (© 2020 Japanese Society of Neuropathology.) more...- Published
- 2020
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30. CogEvo, a cognitive function balancer, is a sensitive and easy psychiatric test battery for age-related cognitive decline.
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Ichii S, Nakamura T, Kawarabayashi T, Takatama M, Ohgami T, Ihara K, and Shoji M
- Subjects
- Adult, Aged, Aged, 80 and over, Dementia diagnosis, Female, Geriatric Assessment, Humans, Japan, Male, Mental Status and Dementia Tests, Middle Aged, Sensitivity and Specificity, Cognition, Cognitive Dysfunction diagnosis, Diagnosis, Computer-Assisted standards
- Abstract
Aim: We examined whether a newly developed computer-aided neuropsychiatric series of test, CogEvo, is necessary and sufficient for the evaluation of cognitive function in older people., Methods: A total of 272 participants in worthwhile life activity for the prevention of decline in mobility and cognitive function were administered tests every week at 33 locations in Fukaura-machi, Japan. Basic profile information, a Mini-Mental State Examination (MMSE), a CogEvo and a clock drawing test were used in the present study., Results: Our results are summarized as: (i) the total score of the CogEvo and MMSE tests decreased significantly according to age and in age group analysis; (ii) scores from the CogEvo and MMSE tests showed a significant correlation; (iii) MMSE scores showed marked ceiling effects; (iv) analysis of cognitive domains, such as orientation, attention, memory and executive function, and spatial cognition using CogEvo showed significant age-dependent impairment; (v) CogEvo discriminated three score groups of MMSE results with sensitivity and specificity of 70% and 60% in the <23 score group, 78% and 54% in the 24-26 score group, and 85% and 70% in the >27 score group, respectively; (vi) CogEvo memory tests reflected more detailed recall function than registration function; and (vii) CogEvo spatial cognition test results were correlated with test items of the MMSE and clock drawing tests., Conclusions: CogEvo is an easy and potentially useful computer-aided test battery that can be used to evaluate age-related or pathological decline in cognitive function from middle age and in preclinical stages of dementia. Geriatr Gerontol Int 2019; ••: ••-••., (© 2019 Japan Geriatrics Society.) more...
- Published
- 2020
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31. A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology.
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Abe K, Shang J, Shi X, Yamashita T, Hishikawa N, Takemoto M, Morihara R, Nakano Y, Ohta Y, Deguchi K, Ikeda M, Ikeda Y, Okamoto K, Shoji M, Takatama M, Kojo M, Kuroda T, Ono K, Kimura N, Matsubara E, Osakada Y, Wakutani Y, Takao Y, Higashi Y, Asada K, Senga T, Lee LJ, and Tanaka K more...
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease psychology, Amyloid beta-Peptides blood, Aniline Compounds, Cognitive Dysfunction psychology, Female, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Positron-Emission Tomography, Predictive Value of Tests, Reference Values, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Thiazoles, tau Proteins blood, Alzheimer Disease blood, Biomarkers blood, Cognitive Dysfunction blood, Peptides blood
- Abstract
Background: Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer's disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established., Objective: We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology., Methods: With only 1.5μl of serum, we examined a new target plate "BLOTCHIP®" plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n = 100), MCI (n = 60), and AD (n = 99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains., Results: Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p < 0.001). MMSE score was well correlated to brain Aβ deposition and to SPD of AD. The mother proteins of the four peptides were upregulated for coagulation, complement, and plasticity (three proteins), and was downregulated for anti-inflammation (one protein) in AD brains., Conclusion: The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage. more...
- Published
- 2020
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32. Astrocytic tau pathologies in aged human brain.
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Okamoto K, Amari M, Fukuda T, Suzuki K, and Takatama M
- Subjects
- Aged, Aged, 80 and over, Astrocytes chemistry, Brain Chemistry, Female, Humans, Male, tau Proteins analysis, Aging pathology, Astrocytes pathology, Brain pathology, Tauopathies pathology
- Abstract
Argyrophilic and tau-positive abnormal structures in astrocytes are frequent in aged brains, with a new nomenclature of aging-related tau astrogliopathy (ARTAG) proposed. The two major cytomorphologies of ARTAG are thorn-shaped astrocytes (TSA) and granular or fuzzy tau immunoreactivity in processes of astrocytes (GFA). We selected 28 cases in which many AT8-identified astrocytic tauopathies were observed in the central nervous system from 330 routine aged autopsied cases, including Alzheimer's disease. AT8-identified and Gallyas silver staining-positive TSA were observed in subpial, subependymal, perivascular areas as well as white matter. These TSA were 4-repeat (4R) tau-positive. In contrast, 3-repeat (3R)-tau was negative in TSA, but positive in short thick cell processes, likely neuropil threads, in subpial and subependymal areas. The frequency of 3R-tau-positive processes was variable. Small dot-like AT8-identified astrocytic processes surrounding vessels in the neuropil were also positive for 4R-tau, but negative for 3R-tau. GFA in cerebral gray matter were AT8-identified and Gallyas-positive, and positive for 4R-tau but negative for 3R-tau. In this study, we did not identify 3R-tau+/4R-tau+ or 3R-tau+/4R-tau- astrocytes. Further studies are needed to clarify the nature and progression of glial tau-positive structures in ARTAG., (© 2019 Japanese Society of Neuropathology.) more...
- Published
- 2019
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33. Gullibility may be a warning sign of Alzheimer's disease dementia.
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Yamaguchi T, Maki Y, Takatama M, and Yamaguchi H
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease etiology, Alzheimer Disease psychology, Cognition physiology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction psychology, Disease Progression, Female, Humans, Male, Mental Status and Dementia Tests, Neuropsychological Tests, Theory of Mind, Alzheimer Disease diagnosis, Cognitive Dysfunction complications, Deception, Geriatric Assessment methods
- Abstract
ABSTRACTBackground:Theory of Mind reasoning, which plays a pivotal role in social interaction, is required to detect deception. Empirically, those with cognitive decline are vulnerable to deception., Methods: Participants were 45 healthy elderly adults with clinical dementia rating (CDR) 0, and 76 outpatients: 25 with amnestic mild cognitive impairment (aMCI, CDR 0.5), 34 with mild Alzheimer's disease dementia (ADD, CDR 1), and 17 with moderate ADD (CDR 2). The task consisted of two single-frame cartoons that depicted a character with an intention to deceive another character using social signs of gaze and pointing, and participants are provided clue questions to detect the character's intentions., Results: The percentage of participants who detected the character's intention decreased with ADD progression (CDR 0, 82.2%; CDR 0.5, 48.0%; CDR 1, 29.4%; and CDR 2, 0%). Total score (0-6) also decreased with ADD progression (CDR 0, 4.4 +/-1.1; CDR 0.5, 3.0 +/-1.3; CDR 1, 2.9 +/-1.5; and CDR 2, 1.6 +/-0.9)., Discussion and Conclusions: The present study demonstrated that those with aMCI have difficulty in detecting other's deceiving intentions, when the intention was shown implicitly using social signs. In a previous study, we have reported that mild ADD showed difficulties in detecting intention, while aMCI succeeded in detection when the intention was depicted explicitly. These results together suggested that those with aMCI is vulnerable to deception when the intention was shown implicitly using non-verbal cues, while ADD may fail to detect the intention even when the intention was shown explicitly. more...
- Published
- 2019
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34. Adult moyamoya disease associated with abundant phosphorylated tau accumulation in the brainstem: Report of a case with autopsy findings.
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Okamoto K, Naito I, Fukuda T, Suzuki K, and Takatama M
- Subjects
- Aged, Asian People, Brain Stem blood supply, Female, Humans, Japan, Moyamoya Disease complications, Moyamoya Disease metabolism, Phosphorylation, Tauopathies complications, Brain Stem pathology, Moyamoya Disease pathology, Tauopathies pathology, tau Proteins metabolism
- Abstract
We report the case of a 72-year-old Japanese woman with moyamoya disease (MMD). She experienced her first intracerebral hemorrhage (ICH) at the age of 32 years, and had nine ICHs and/or intraventricular hemorrhages during the following 40 years. Cerebral angiograms and vascular pathologies at autopsy confirmed that the patient suffered from MMD. Macroscopically, there were brown-colored changes in the subarachnoid space, mainly at the base of the brain and around the cerebellar hemispheres. Microscopically, hemosiderin deposits were observed mainly in the old hemorrhagic lesions and on the surface of the brainstem and cerebellum. Many AT8-immunoreactive neurons and neurites were observed in the pons and midbrain, mainly in the locus ceruleus and reticular formation in the midbrain. Several AT8-immunoreactive neurons and neurites were positive for Gallyas silver staining. A few tiny and short AT8-immunoreactive processes were observed in the molecular, Purkinje cell and granular layers of the cerebellum. There were a few phosphorylated tau accumulations in the cerebrum without senile plaques. Lewy pathologies and transactive response DNA-binding protein 43 kDa proteinopathy were not detected. We suspect that oxidative stress after repeated bleedings with long-term courses in the ventricles and subarachnoid space may accelerate phosphorylated tau accumulation in the brainstem. To our knowledge, this is the first report of MMD with tauopathy in the brainstem., (© 2017 Japanese Society of Neuropathology.) more...
- Published
- 2018
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35. Comparison of AT8 immunoreactivity in the locus ceruleus and hippocampus of 154 brains from routine autopsies.
- Author
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Okamoto K, Amari M, Fukuda T, Suzuki K, and Takatama M
- Subjects
- Adult, Aged, Aged, 80 and over, Autopsy, Female, Humans, Male, Middle Aged, Neurofibrillary Tangles pathology, Phosphorylation, Hippocampus pathology, Locus Coeruleus pathology, Neurons pathology, tau Proteins analysis
- Abstract
We compared semiquantitatively AT8 immunoreactivity in the locus ceruleus (LC) and hippocampus of 154 brains from routine autopsies to investigate the initial sites of phosphorylated tau (phospho-tau) development. The numbers of AT8-positive neurons and the severity of AT8-positive neuropil threads (NTs) in the LC were strongly associated: there were no cases with AT8-positive neurons that lacked NTs and 20 cases (13%) had only NTs in the LC. Phospho-tau pathologies in the LC were almost equally on both sides, although some cases (7.8%) showed unilateral predominance. The numbers of AT8-positive neurons in the LC and the numbers of AT8-positive neurons and NTs in the hippocampus were also strongly associated. There were only two cases with AT8-positive neurons in the LC that lacked phospho-tau pathology in the hippocampus, and 21 cases (13.6%) with phospho-tau pathology in the hippocampus that lacked AT8-positive neurons in the LC. The numbers of AT8-positive NTs in the LC and AT8-positive neurons and NTs in the hippocampus were also strongly associated. There were seven cases (4.5%) with AT8-positive NTs in the LC that lacked phospho-tau pathology in the hippocampus, and five cases (3.2 %) with phospho-tau pathologies in the hippocampus that lacked AT8-positive NTs in the LC. In this study, we could not confirm that phospho-tau pathologies begin in the LC. We suspect their simultaneous occurrences in both hippocampal regions and in LC., (© 2017 Japanese Society of Neuropathology.) more...
- Published
- 2017
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36. Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains.
- Author
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Nagamine S, Yamazaki T, Makioka K, Fujita Y, Ikeda M, Takatama M, Okamoto K, Yokoo H, and Ikeda Y
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease pathology, Brain pathology, Humans, Male, Middle Aged, Phosphorylation, Vacuoles pathology, Alzheimer Disease metabolism, Brain metabolism, Neurofibrillary Tangles metabolism, Sialic Acids metabolism, Vacuoles metabolism, tau Proteins metabolism
- Abstract
Glycosylation is one of the major post-translational modifications of proteins. The status of sialylation of the neuropathological hallmarks of various neurodegenerative disorders was investigated in this study. Here, we report the novel findings that two phosphorylated tau (p-tau)-containing structures associated with Alzheimer's disease (AD), that is, neurofibrillary tangles (NFTs) and granulovacuolar degenerations (GVDs), were hypersialylated. The NFTs, GVDs and dystrophic neurites of senile plaques (SPs) in AD hippocampi were clearly visualized by immunohistochemistry using an anti-sialic acid (SA) antibody. In contrast, the amyloid core of SPs was not sialylated at all. Interestingly, other p-tau-containing structures, that is, globose-type NFTs in progressive supranuclear palsy and Pick bodies and ballooned neurons in frontotemporal lobar degeneration with Pick bodies, were also hypersialylated. Unlike the p-tau-containing structures observed in tauopathies, the hallmarks of other neurodegenerative disorders, such as Lewy bodies in Parkinson's disease, glial cytoplasmic inclusions in multiple system atrophy, Bunina bodies, skein-like inclusions and round inclusions in amyotrophic lateral sclerosis, intranuclear inclusions in neuronal intranuclear inclusion disease and physiological bodies or granules (lipofuscin granules, corpora amylacea and melanin granules), were not immunolabeled by the anti-SA antibody. Because this antibody specifically identified NFTs and GVDs, immunostaining for sialylation represents a useful tool to screen these structures in a diagnostic setting. These results clearly indicate that the pathological hallmarks of various tauopathies are commonly hypersialylated, and that sialylation plays an important role in the process of p-tau accumulation in AD and other tauopathies., (© 2015 Japanese Society of Neuropathology.) more...
- Published
- 2016
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37. Immunolocalization of Tom1 in relation to protein degradation systems in Alzheimer's disease.
- Author
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Makioka K, Yamazaki T, Takatama M, Ikeda M, Murayama S, Okamoto K, and Ikeda Y
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease physiopathology, Amyloid beta-Peptides metabolism, Brain pathology, Female, Humans, Intracellular Signaling Peptides and Proteins metabolism, Lysosomal-Associated Membrane Protein 2 metabolism, Male, Middle Aged, Neurites metabolism, Neurofibrillary Tangles pathology, Neurons pathology, Ubiquitins metabolism, Ventricular Myosins metabolism, tau Proteins metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, Brain metabolism, Proteins metabolism, Proteolysis
- Abstract
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Its pathological hallmarks are senile plaques (SPs), which contain extracellular deposits of amyloid β (Aβ) protein fibrils and dystrophic neurites (DNs), and neurofibrillary tangles (NFTs) containing hyperphosphorylated tau. Impairment of protein-degradation systems, including the ubiquitin-proteasome and the autophagy-lysosome systems, has been proposed as one of the causes of the accumulation of these aberrant proteins in AD brains. Tom1 (target of Myb1) was originally identified by the induction of its expression by the v-Myb oncogene and is a part of two major protein-degradation systems. The present study was conducted by immunohistochemical and immunofluorescent stainings to show that Tom1 was localized in DNs, perisomatic granules (PSGs), and NFTs in AD brains. Moreover, in DNs, Tom1 colocalized with ubiquitin, lysosomal proteins, and Tom1-related proteins (Tollip and myosin VI), which act in both protein-degradation systems via Tom1. These results indicate that Tom1 plays important roles in protein-degradation systems in AD pathogenesis., (Copyright © 2016 Elsevier B.V. All rights reserved.) more...
- Published
- 2016
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38. An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation.
- Author
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Okamoto K, Fujita Y, Hoshino E, Tamura Y, Fukuda T, Hasegawa M, and Takatama M
- Subjects
- Amyotrophic Lateral Sclerosis pathology, Hippocampus pathology, Humans, Male, Middle Aged, Mutation, Neurons pathology, Amyotrophic Lateral Sclerosis genetics, Anterior Horn Cells pathology, DNA-Binding Proteins genetics, Inclusion Bodies pathology, Spinal Cord pathology
- Abstract
We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked-in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation-dependent transactivation response DNA-binding protein of 43 kDa (pTDP-43)-positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin- and p62-positive inclusions was markedly lower than that of pTDP-43-positive inclusions. NCIs and many fine dot-like pTDP-43-positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti-pTDP-43 antibody was slightly different from previous TDP-43 pathological subtypes., (© 2015 Japanese Society of Neuropathology.) more...
- Published
- 2015
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39. Cytoplasmic TDP-43 accumulation in cells of the adrenal medulla in individuals with or without amyotrophic lateral sclerosis.
- Author
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Okamoto K, Amari M, Fujita Y, Makioka K, Fukuda T, Suzuki K, and Takatama M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cytoplasm chemistry, Female, Humans, Inclusion Bodies metabolism, Inclusion Bodies pathology, Male, Middle Aged, Phosphorylation, Young Adult, Adrenal Medulla metabolism, Adrenal Medulla pathology, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, DNA-Binding Proteins metabolism
- Abstract
The transactive response DNA-binding protein of 43 kDa (TDP-43) is normally located predominantly in the nucleus, whereas pathological TDP-43 is mostly found in the cytoplasm. Cytoplasmic TDP-43 accumulation has not yet been reported in normal general organs. In our preliminary study, paraffin sections of the general organs of individuals with or without amyotrophic lateral sclerosis (ALS) were immunostained with antibodies against TDP-43 and phosphorylated TDP-43 (pTDP-43). Diffuse and granular immunostaining pattern of TDP-43 and pTDP-43 were observed frequently in the cytoplasm of renal tubular cells, and less frequently in the cells of several organs; however, the majority of these immunoreactivities were nonspecific biotin reactions. Conversely, many TDP-43-positive and pTDP-43-negative cytoplasmic accumulations were observed in the adrenal medulla in every individual (with or without ALS). Skein-like or round inclusions were not observed. The cells in the adrenal medulla were well preserved, and the cytoplasmic TDP-43 accumulations were frequent in the cells of all routine autopsy cases without loss of nuclear TDP-43 immunostaining; therefore, we considered that this was a physiological phenomenon. This is the first study that demonstrated the cytoplasmic accumulation of TDP-43 in routinely autopsied cases., (© 2014 Japanese Society of Neuropathology.) more...
- Published
- 2014
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40. CSF levels of Aβ1-38/Aβ1-40/Aβ1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease.
- Author
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Ikeda M, Tashiro Y, Takai E, Kurose S, Fugami N, Tsuda K, Arisaka Y, Kodaira S, Fujita Y, Makioka K, Mizuno Y, Shimada H, Harigaya Y, Takatama M, Amari M, Yamazaki T, Yamaguchi H, Higuchi T, Okamoto K, Tsushima Y, and Ikeda Y more...
- Subjects
- Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Aphasia, Primary Progressive diagnostic imaging, Aphasia, Primary Progressive genetics, Apolipoproteins E genetics, Biomarkers cerebrospinal fluid, Humans, Language Tests, Positron-Emission Tomography, Alzheimer Disease cerebrospinal fluid, Amyloid beta-Peptides cerebrospinal fluid, Aphasia, Primary Progressive cerebrospinal fluid
- Abstract
Primary progressive aphasia (PPA) is a cognitive syndrome characterized by progressive and isolated language impairments due to neurodegenerative diseases. Recently, an international group of experts published a Consensus Classification of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24 patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT, (11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181, Aβ1-42, Aβ1-40 and Aβ1-38), to elucidate relationships between neuroimaging studies and biochemical findings in the three PPA clinical variants. Cognitive and speech functions were measured by mini-mental state examination and standard language test of aphasia. The patients with lvPPA showed significant decreases in CSF Aβ1-42 and ratios of Aβ1-42/Aβ1-40 and Aβ1-42/Aβ1-38, and significant increases in CSF ptau-181 and ratios of ptau-181/Aβ1-42 and ptau-181/Aβ1-38; these findings were similar to those of patients with Alzheimer's disease (AD). We observed a higher frequency of the ApoE ε4 allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB-PET of lvPPA patients, PiB positive findings were detected in cortices of frontal, temporal and parietal lobes and the posterior cingulate, where massive Aβ may accumulate due to AD. Our results of AD-CSF markers including Aβ1-38 and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological mechanism with the occurrence of AD. more...
- Published
- 2014
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41. Immunolocalization of Smurf1 in Hirano bodies.
- Author
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Makioka K, Yamazaki T, Takatama M, Ikeda M, and Okamoto K
- Subjects
- Aged, Aged, 80 and over, Female, HeLa Cells, Hippocampus pathology, Humans, Inclusion Bodies pathology, Male, Middle Aged, Ubiquitin-Protein Ligases physiology, Alzheimer Disease pathology, Hippocampus chemistry, Inclusion Bodies chemistry, Ubiquitin-Protein Ligases analysis
- Abstract
The Smad ubiquitination regulatory factor 1 (Smurf1) is one of the E3 ubiquitin ligases and is related to multiple biological processes. Despite the various roles played by this protein, there is no report on the function of Smurf1 in neurodegeneration. Hirano bodies (HBs) are intracellular structures within neuronal processes and were first described in the hippocampus of individuals with amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam. In addition, the number of HBs increases in the brains of patients with Alzheimer's disease (AD) compared with age-matched non-demented control individuals. In this study, we immunohistochemically demonstrated that Smurf1 localized in HBs in the brains of patients with AD by using plural anti-Smurf1 antibodies, and Smurf1 co-localized with HBs marker proteins by using confocal microscopy. Moreover, we demonstrated that Smurf1 localized in HB-like F-actin aggregates in a cell culture system via treatment with the actin-stabilizing toxin jasplakinolide (jpk). Smurf1 represents a novel protein component of HBs, to be included in an expanding list of HB-associated proteins., (© 2013. Published by Elsevier B.V. All rights reserved.) more...
- Published
- 2014
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42. Pathogenesis of focal cytoplasmic necrosis of the smooth muscle cells in hypertensive rat arterial media.
- Author
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Suzuki K, Sakata N, Hiraishi K, Mori I, and Takatama M
- Abstract
Hypertensive rat arteries exhibited severe medial smooth muscle cell injury and necrosis. Electron microscopic observations showed the smooth muscle cells of these arteries exhibited characteristics of focal cytoplasmic necrosis forming new cytodemarcating membrane between the healthy cytoplasm and necrotic cytoplasm. When the focal necrotic cytoplasm disappeared from the injured smooth muscle cells, it left it with a moth-eaten leaf-like appearance (moth-eaten necrosis). At an advanced stage of injury, smooth muscle cells changed to islet-like cell bodies with newly formed basement membranes around them, and further islet-like cell bodies and cell debris disappeared leaving lamellar and reticular basement membranes. In hypertensive rats injected with nitroblue tetrazolium (NBT), formazan deposits were observed in the medial cells and nitrotyrosine, a biomarker of peroxynitrite, were immunohistochemically observed in the arterial media. Nick-end positive extranuclear small granular bodies, which might have derived from focal necrotic cytoplasm and nucleus, were detected in the arterial media using DNA nick-end labeling method. Based on electron microscopical and histochemical findings, we conjectured that the focal cytoplasmic necrosis of the smooth muscle cells in the arterial media depended on injury arising from mitochondria-derived oxidants. more...
- Published
- 2014
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43. Accumulation of phosphorylated TDP-43 in the CNS of a patient with Cockayne syndrome.
- Author
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Sakurai A, Makioka K, Fukuda T, Takatama M, and Okamoto K
- Subjects
- Adolescent, Adult, Age of Onset, Astrocytes metabolism, Astrocytes pathology, Child, Child, Preschool, DNA-Binding Proteins metabolism, Fluorescent Antibody Technique, Humans, Inclusion Bodies metabolism, Inclusion Bodies pathology, Male, Phosphorylation, Young Adult, Brain metabolism, Brain pathology, Cockayne Syndrome metabolism, Cockayne Syndrome pathology, TDP-43 Proteinopathies metabolism, TDP-43 Proteinopathies pathology
- Abstract
Here, we report a case of Cockayne syndrome (CS) in a Japanese man who displayed a unique pathology of phosphorylated trans-activation response (TAR) DNA-binding protein 43 (pTDP-43) with abundant Rosenthal fibers. Many round pTDP-43-positive structures were detected throughout the CNS; however, most of them were located in two regions that also exhibited neuronal depletion: the cerebellar cortex and the inferior olivary nucleus. To a lesser extent, these aggregates were also present in the cerebellar white matter, around the subependymal regions in the brain stem, and in the spinal cord. Intraneuronal pTDP-43 inclusions were only observed in a small number of neurons in the inferior olivary nucleus. Double-label immunofluorescence revealed that many of the aggregates were localized to astrocytes. The observed distribution and the morphology of the pTDP-43-positive structures were unique and have not yet been reported. Therefore, a pTDP-43-related pathology may be implicated in CS as well as in other neurodegenerative diseases such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Whether the pathology of these diseases reflects a primary neurodegenerative process or a secondary reaction is not known., (© 2013 Japanese Society of Neuropathology.) more...
- Published
- 2013
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44. Reduced expression of BTBD10 in anterior horn cells with Golgi fragmentation and pTDP-43-positive inclusions in patients with sporadic amyotrophic lateral sclerosis.
- Author
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Furuta N, Makioka K, Fujita Y, Ikeda M, Takatama M, Matsuoka M, and Okamoto K
- Subjects
- Aged, Aged, 80 and over, Anterior Horn Cells pathology, DNA-Binding Proteins metabolism, Female, Golgi Apparatus pathology, Humans, Immunohistochemistry, Inclusion Bodies pathology, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, Anterior Horn Cells metabolism, Golgi Apparatus metabolism, Inclusion Bodies metabolism, Nuclear Proteins biosynthesis
- Abstract
Overexpression of BTBD10 (BTB/POZ domain-containing protein 10) suppresses G93A-superoxide dismutase 1 (SOD1)-induced motor neuron death in a cell-based amyotrophic lateral sclerosis (ALS) model. In the present study, paraffin sections of spinal cords from 13 patients with sporadic ALS and 10 with non-ALS disorders were immunostained using a polyclonal anti-BTBD10 antibody. Reduced BTBD10 expression in the anterior horn cells was more frequent in spinal cords from ALS patients than in cords from patients with non-ALS disorders. We further investigated the relationship between the level of BTBD10 immunoreactivity and the morphology of the Golgi apparatus (GA) and the presence of phosphorylated TAR-DNA-binding protein 43 (pTDP-43). Mirror sections of spinal cords from five sporadic ALS cases were immunostained with antibodies against BTBD10 and trans-Golgi-network (TGN)-46 or pTDP-43. Whereas 89.7-96.5% of the neurons with normal BTBD10 immunoreactivity showed normal GA morphology and no pTDP-43 cytoplasmic aggregates, 86.2-94.3% of the neurons with reduced BTBD10 expression showed GA fragmentation and abnormal pTDP-43 aggregates. These findings suggest that reduced BTBD10 expression is closely linked to the pathogenesis of sporadic ALS., (© 2013 Japanese Society of Neuropathology.) more...
- Published
- 2013
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45. Cerebrospinal fluid levels of phosphorylated tau and Aβ1-38/Aβ1-40/Aβ1-42 in Alzheimer's disease with PS1 mutations.
- Author
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Ikeda M, Yonemura K, Kakuda S, Tashiro Y, Fujita Y, Takai E, Hashimoto Y, Makioka K, Furuta N, Ishiguro K, Maruki R, Yoshida J, Miyaguchi O, Tsukie T, Kuwano R, Yamazaki T, Yamaguchi H, Amari M, Takatama M, Harigaya Y, and Okamoto K more...
- Subjects
- Adult, Apolipoprotein E2 genetics, Dementia cerebrospinal fluid, Dementia genetics, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Phosphorylation, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease genetics, Amyloid beta-Peptides cerebrospinal fluid, Biomarkers cerebrospinal fluid, Mutation genetics, Presenilin-1 genetics, tau Proteins cerebrospinal fluid
- Abstract
We studied seven cases of Alzheimer's disease (AD). Six of the patients had presenilin 1 (PS1) mutations (PS1AD). Three novel PS1 mutations (T99A, H131R and L219R) and three other missense mutations (M233L, H163R and V272A) were found in the PS1AD group. We measured the levels of phosphorylated tau (ptau-181, ptau-199) and Aβ (Aβ1-42, Aβ1-40 and Aβ1-38) in the cerebrospinal fluid (CSF) of PS1AD patients, early-onset sporadic AD (EOSAD), late-onset sporadic AD (LOSAD) and non-demented subjects (ND). The CSF levels of Aβ1-42 in the three AD groups were significantly lower than those of the ND group (p < 0.0001). CSF levels of Aβ1-42 in the PS1AD group were significantly lower than those in the two sporadic AD groups. The Aβ1-40 and Aβ1-38 levels in the CSF of the PS1AD group were significantly lower than those of the three other groups (p < 0.0001, respectively). The levels of Aβ1-40, Aβ1-38 and Aβ1-42 in the CSF of the PS1AD group remained lower than those of the ND group for 4 years. Not only CSF Aβ1-42, but also Aβ1-40 and Aβ1-38 decreased in the advanced stages of PS1AD. more...
- Published
- 2013
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46. Encephalopathy with amyloid angiopathy and numerous amyloid plaques with low levels of CSF Aβ1-40/Aβ1-42.
- Author
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Ikeda M, Hirayanagi K, Arai M, Kakuda S, Makioka K, Furuta N, Takai E, Kasahara H, Tsukagoshi S, Fujita Y, Amari M, Takatama M, Nakazato Y, and Okamoto K
- Subjects
- Apolipoproteins E genetics, Biopsy, Brain Diseases, Metabolic complications, Brain Diseases, Metabolic metabolism, Cerebral Amyloid Angiopathy complications, Cerebral Amyloid Angiopathy metabolism, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Occipital Lobe metabolism, Occipital Lobe pathology, Plaque, Amyloid cerebrospinal fluid, Temporal Lobe metabolism, Temporal Lobe pathology, Amyloid beta-Peptides cerebrospinal fluid, Brain Diseases, Metabolic pathology, Cerebral Amyloid Angiopathy pathology, Peptide Fragments cerebrospinal fluid, Plaque, Amyloid pathology
- Abstract
A middle-aged male suffering from encephalopathy with cerebral amyloid angiopathy (CAA) with amyloid beta (Aβ) presented with initial symptoms of transient consciousness disturbance and left visual field photophobia. Lesions with aberrantly high signal on T2-weighted magnetic resonance imaging (MRI) of the brain appeared in the right temporal lobe posterior to the occipital lobe and spread to other areas. Brain biopsy revealed Aβ deposits in vascular walls and numerous diffuse plaques in parenchymal areas. Based on MRI findings, Initial corticosteroid therapy with beta methasone effectively improved the neurological symptoms of consciousness disturbance and motor deficits. After corticosteroid therapy was stopped at 4 weeks, recurrence occurred. Additional corticosteroids did not improve clinical symptoms and the patient progressed to a bed-ridden state with a severe consciousness disturbance. Notably, CSF Aβ1-42 and CSF Aβ1-40 decreased while the recurrent encephalopathy worsened. After intense deterioration, the patient became stable. CSF Aβ1-42 increased but remained at a very low level. This case of CAA encephalopathy with apolipoprotein E ϵ4/ϵ4 homozygosity showed Aβ deposits in vascular walls and numerous diffuse plaques in parenchymal areas. The clinical course suggests that reduction of CSF Aβ1-42 and Aβ1-40 might be related to clinical deterioration in cases of encephalopathy. more...
- Published
- 2012
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47. Comparison of phosphorylated TDP-43-positive inclusions in oculomotor neurons in patients with non-ALS and ALS disorders.
- Author
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Mizuno Y, Fujita Y, Takatama M, and Okamoto K
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Neurons chemistry, Oculomotor Nerve chemistry, Oculomotor Nerve pathology, Phosphorylation physiology, Young Adult, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, DNA-Binding Proteins biosynthesis, Inclusion Bodies metabolism, Inclusion Bodies pathology, Neurons metabolism, Neurons pathology, Oculomotor Nerve metabolism
- Abstract
TDP-43 has been identified as a major component of the pathological inclusions in most forms of frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis (ALS). In the present study, paraffin sections of the midbrain in 112 patients with various non-ALS disorders and 27 patients with sporadic ALS were immunostained with antibody against phosphorylated TDP-43 (pTDP-43). pTDP-43-positive inclusions in oculomotor neurons were detected in 18 of 112 patients with non-ALS disorders (16.1%). The appearance of the inclusions showed fine filamentous structures rather than the skein-like inclusions seen in the anterior horn cells of ALS spinal cords. The incidence was increased in the age range of 80-89 years old (10/37 cases; 27.0%), in which 6 of 10 cases demonstrated AD pathology in the temporal lobes. Twenty-seven ALS patients were examined and the findings were compared with those of non-ALS patients. There were 13 cases demonstrating pTDP-43-positive inclusions (48.1%) which showed stronger immunoreactivities in ALS cases. This is the first report demonstrating fine filamentous pTDP-43-positive inclusions in oculomotor neurons in non-ALS disorders. Although the mechanisms underlying pTDP-43 in oculomotor neurons are currently unknown, its detection is of interest, and the expression may occur not only in ALS but also during the aging process., (Copyright © 2011 Elsevier B.V. All rights reserved.) more...
- Published
- 2012
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48. Activation and alteration of lysosomes in multiple system atrophy.
- Author
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Makioka K, Yamazaki T, Takatama M, Nakazato Y, and Okamoto K
- Subjects
- Case-Control Studies, Female, Humans, Immunohistochemistry, Lysosomal-Associated Membrane Protein 2, Male, Middle Aged, Multiple System Atrophy metabolism, Cathepsin D metabolism, Hexosaminidases metabolism, Lysosomal Membrane Proteins metabolism, Lysosomes pathology, Multiple System Atrophy pathology
- Abstract
Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder. Its histopathological features include glial cytoplasmic inclusions that contain α-synuclein as the main component. Recently, multiple lines of evidence have suggested a role for lysosomes in the pathogenesis of many neurodegenerative diseases. To elucidate whether lysosomes are also implicated in the pathology of MSA, we carried out an immunohistochemical study using antibodies against lysosomal proteins in the brains of patients with MSA and in control brains. A robust increase in the expression and an alteration in the morphology and distribution of lysosomal-protein-positive structures were observed in MSA brains. Double immunohistochemistry demonstrated that lysosomal markers did not colocalize mainly with glial cytoplasmic inclusions, but colocalized with a microglial marker. These immunohistochemical signatures suggest that lysosomes are activated in microglia during the disease process, and play a pivotal role in the pathology of MSA. more...
- Published
- 2012
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49. Optineurin in neurodegenerative diseases.
- Author
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Osawa T, Mizuno Y, Fujita Y, Takatama M, Nakazato Y, and Okamoto K
- Subjects
- Cell Cycle Proteins, Humans, Immunohistochemistry, Inclusion Bodies pathology, Membrane Transport Proteins, Neurodegenerative Diseases pathology, Transcription Factor TFIIIA analysis, Biomarkers analysis, Inclusion Bodies metabolism, Neurodegenerative Diseases metabolism, Transcription Factor TFIIIA metabolism
- Abstract
Optineurin is a gene associated with normal tension glaucoma and primary open-angle glaucoma, one of the major causes of irreversible bilateral blindness. Recently, mutations in the gene encoding optineurin were found in patients with amyotrophic lateral sclerosis (ALS). Immunohistochemical analysis showed aggregation of optineurin in skein-like inclusions and round hyaline inclusions in the spinal cord, suggesting that optineurin appears to be a more general marker for ALS. However, our detailed examinations demonstrated that optineurin was found not only in ALS-associated pathological structures, but also in ubiquitin-positive intraneuronal inclusions in ALS with dementia, basophilic inclusions in the basophilic type of ALS, neurofibrillary tangles and dystrophic neurites in Alzheimer's disease, Lewy bodies and Lewy neurites in Parkinson's disease, ballooned neurons in Creutzfeldt-Jakob disease, glial cytoplasmic inclusions in multiple system atrophy, and Pick bodies in Pick disease. With respect to optineurin-positive basophilic inclusions, these structures showed variable immunoreactivities for ubiquitin; some structures were obviously ubiquitin-positive, while others were negative for the protein, suggesting that optineurin expression was not always associated with the expression of ubiquitin. This study indicates that optineurin is widely distributed in neurodegenerative conditions; however, its significance is obscure., (© 2011 Japanese Society of Neuropathology.) more...
- Published
- 2011
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50. Numerous FUS-positive inclusions in an elderly woman with motor neuron disease.
- Author
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Fujita Y, Fujita S, Takatama M, Ikeda M, and Okamoto K
- Subjects
- Aged, Autopsy, Female, Humans, Immunohistochemistry, Inclusion Bodies genetics, Inclusion Bodies metabolism, Motor Neuron Disease genetics, Motor Neuron Disease metabolism, Polymerase Chain Reaction, RNA-Binding Protein FUS genetics, Inclusion Bodies pathology, Motor Neuron Disease pathology, RNA-Binding Protein FUS metabolism
- Abstract
We report an autopsy case of a 75-year-old Japanese woman with motor neuron disease (MND) showing numerous neuronal and glial inclusions immunostained with anti-fused in sarcoma (FUS) antibody. At 73 years, she received a diagnosis of MND and died of respiratory insufficiency 2 years later. No mutation was found in all exons of the FUS gene. Neuropathological examination revealed a reduced number of anterior horn cells and degeneration of the pyramidal tracts. Neither Bunina bodies nor inclusions positive for ubiquitin/phosphorylated TAR DNA binding protein of 43 kD (pTDP-43), such as skein-like or round inclusions, were observed. However, basophilic inclusions (BIs) were frequently observed in the remaining neurons of the anterior horns, facial nuclei, hypoglossal nuclei, vestibular nuclei, dentate nuclei and inferior olivary nuclei. In an immunohistochemical analysis, the BIs showed strong immunoreactivity with anti-FUS and anti-ubiquitin-binding protein p62 (p62) antibodies. The nuclear staining of FUS was preserved in some neurons with FUS-positive inclusions, and a few FUS-positive glial inclusions were found. FUS-positive inclusions were more common than p62-positive inclusions in some anatomical regions, and in some neurons, p62 immunoreactivity was observed in only parts of the BIs. These results suggest that BI formation and TDP-43 aggregation have different pathogenic mechanisms, and FUS may play an important role in the pathogenesis of MND with BIs. This patient has the oldest reported age of onset for MND with BIs, and clinical features observed in this patient were indistinguishable from those of classic sporadic MND. Therefore, we consider that the age of onset and clinical features of FUS-related disorders may be variable., (© 2010 Japanese Society of Neuropathology.) more...
- Published
- 2011
- Full Text
- View/download PDF
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