Kunimasa Arima

National Center of Neurology and Psychiatry, Кодаиры, Tōkyō, Japan

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Publications (116)519.69 Total impact

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    ABSTRACT: The Gallyas method is a silver impregnation technique that is essential in the field of neuropathology because of its high sensitivity for the detection of argentophilic inclusion bodies in the central nervous system. In Japan, the Gallyas method has improved and is widely used as the “modified Gallyas method”. However, this method is not popularly used in general pathology laboratories because of the need for special reagents, several staining processes, and skilled techniques. The objective of the current study was to provide a simplified Gallyas method. We omitted the lanthanum nitrate step from the staining process and verified the adequacy in comparison with the original method as well as immunohistochemistry, using specimens from patients of Alzheimer's disease, argyrophilic grain disease, multiple system atrophy, Pick's disease, and Lewy body disease. The simplified method provided good staining to all the structures in archival tissues, compared with the modified Gallyas method in a significantly shorter staining time. The lanthanum nitrate step can be omitted from the modified Gallyas method, resulting in reduction in the number of reagents required and shortening of the staining time.
    Neuropathology 09/2014; · 1.91 Impact Factor
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    ABSTRACT: While research on remission in schizophrenia has gained attention, personality characteristics associated with remission in schizophrenia have been under-studied. A functional valine-to-methionine (Val158Met) polymorphism in the catechol-O-methyltransferase (COMT) gene is shown to modify clinical presentation of schizophrenia despite weak or no association with the disorder itself. Studies also report that this polymorphism can affect personality traits. We aimed to examine personality traits of remitted patients with schizophrenia as compared to symptomatic patients and healthy controls and to investigate whether the COMT Val158Met polymorphism influences their personality. Scores on the Temperament and Character Inventory were compared between 34 remitted outpatients with schizophrenia, age- and sex-matched 72 symptomatic outpatients with schizophrenia, and matched 247 healthy individuals. The effect of COMT Val158Met polymorphism on personality was examined in each group. The analysis of covariance, controlling for confounding variables, revealed that compared to healthy controls, symptomatic patients exhibited a pervasively altered personality profile whereas remitted patients showed alterations in more limited personality dimensions and demonstrated normal levels of novelty-seeking, reward dependence and cooperativeness. The two-way analysis of covariance, with genotype and sex as between-subject factors and confounders as covariates, revealed that Met carriers demonstrated significantly lower reward dependence and cooperativeness than Val homozygotes in symptomatic patients; while no significant genotype effect was found in remitted patients or in healthy individuals. These findings indicate that remitted patients with schizophrenia have a relatively adaptive personality profile compared to symptomatic patients. The COMT Val158Met polymorphism might have a modulating effect on the relationship between personality and remission.
    Journal of psychiatric research. 05/2014;
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    ABSTRACT: Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Neuropathologically, NHD exhibits profound loss of myelin and accumulation of axonal spheroids, accompanied by intense gliosis accentuated in the white matter of the frontal and temporal lobes. At present, the molecular mechanism responsible for development of leukoencephalopathy in NHD brains remains totally unknown.
    Orphanet Journal of Rare Diseases 05/2014; 9(1):68. · 4.32 Impact Factor
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    ABSTRACT: TMEM106B is a transmembrane glycoprotein of unknown function located within endosome/lysosome compartments expressed ubiquitously in various cell types. Previously, the genome-wide association study (GWAS) identified a significant association of TMEM106B single nucleotide polymorphisms (SNPs) with development of frontotemporal lobar degeneration with ubiquitinated TAR DNA-binding protein-43 (TDP-43)-positive inclusions (FTLD-TDP), particularly in the patients exhibiting the progranulin (PGRN) gene (GRN) mutations. Recent studies indicate that TMEM106B plays a pathological role in various neurodegenerative diseases, including Alzheimer's disease (AD). However, at present, the precise levels of TMEM106B expression in AD brains remain unknown. By quantitative reverse transcription (RT)-PCR (qPCR), western blot and immunohistochemistry, we studied TMEM106B and PGRN expression levels in a series of AD and control brains, including amyotrophic lateral sclerosis, Parkinson's disease, multiple system atrophy and non-neurological cases. In AD brains, TMEM106B mRNA and protein levels were significantly reduced, whereas PGRN mRNA levels were elevated, compared with the levels in non-AD brains. In all brains, TMEM106B was expressed in the majority of cortical neurons, hippocampal neurons, and some populations of oligodendrocytes, reactive astrocytes and microglia with the location in the cytoplasm. In AD brains, surviving neurons expressed intense TMEM106B immunoreactivity, while senile plaques, neurofibrillary tangles and the perivascular neuropil, almost devoid of TMEM106B, intensely expressed PGRN. We found an inverse relationship between TMEM106B (downregulation) and PGRN (upregulation) expression levels in AD brains, suggesting a key role of TMEM106B in the pathological processes of AD.
    Alzheimer's Research and Therapy 03/2014; 6(2):17. · 4.39 Impact Factor
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    ABSTRACT: The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with (18) F-FDG PET and (99m) Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between (18) F-FDG PET and (99m) Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m) Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between (18) F-FDG PET and (99m) Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on (18) F-FDG PET and (99m) Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of (18) F-FDG PET and (99m) Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 03/2014; · 2.98 Impact Factor
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    ABSTRACT: Objective Inflammasome, activated by pathogen-derived and host-derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase-1 (CASP1) activation and interleukin-1β (IL-1B) maturation. Mice deficient for NLRP3 inflammasome components are resistant to experimental autoimmune encephalomyelitis (EAE), suggesting a pro-inflammatory role of NLRP3 inflammasome. However, at present, a pathological role of NLRP3 inflammasome in multiple sclerosis (MS) brains remains unknown. Methods We studied the expression of NLRP3 inflammasome components in active demyelinating lesions of MS by immunohistochemistry. ResultsReactive astrocytes and perivascular macrophages expressed all three components of NLRP3 inflammasome – NLRP3, ASC and CASP1 – along with IL-1B in active demyelinating lesions of MS, active necrotic lesions of neuromyelitis optica (NMO) and acute necrotic lesions of cerebral infarction. In contrast, the levels of expression of NLRP3, ASC, CASP1, and IL-1B were greatly reduced in chronic inactive lesions of MS and gliotic lesions of cerebral infarction. Furthermore, the great majority of ramified and amoeboid microglia did not express NLRP3 in active and inactive MS lesions. ConclusionsNLRP3 inflammasome could be activated chiefly in reactive astrocytes and infiltrating macrophages under the condition of active destruction of brain tissues that potentially provides a danger signal.
    Clinical and Experimental Neuroimmunology. 12/2013; 4(3).
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    ABSTRACT: Impaired dexterity is a major psychomotor deficit reported in patients with schizophrenia. In the present study, the Purdue pegboard test was used to compare the manual dexterity in patients with schizophrenia and healthy controls. We also examined the influence of antipsychotics, benzodiazepines, and benzodiazepine-like drugs on manual dexterity. Subjects were 93 patients with schizophrenia and 93 healthy controls, matched for sex and age distributions. Control subjects scored significantly higher on all scores of Purdue pegboard than patients with schizophrenia. Age, PANSS negative symptom scale, typical antipsychotic dose, and use of benzodiazepines and/or benzodiazepine-like drugs were negatively correlated with the pegboard scores in patients with schizophrenia. The present results indicate that patients with schizophrenia have impaired gross and fine fingertip dexterity compared to healthy controls. The use of typical antipsychotics and benzodiazepines and/or benzodiazepine-like drugs, but not atypical antipsychotics, had significant negative impact on dexterity in patients with schizophrenia. Psychiatrists should be aware that some psychotropic medications may enhance the disability caused by the impairment of dexterity in patients with schizophrenia.
    Journal of Psychiatric Research 11/2013; · 4.09 Impact Factor
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    Alzheimer's Research and Therapy 07/2013; 5(4):30. · 4.39 Impact Factor
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    ABSTRACT: Recently, neurobiological studies of the cognitive model of depression have become vastly more important, and a growing number of such studies are being reported. However, the relationship between the proportion of positive and negative automatic thought and activity in the prefrontal and temporal cortices has not yet been explored. We examined the relationship between brain activity and the proportion of positive and negative automatic thought in patients with major depressive disorder (MDD), using multi-channel near-infrared spectroscopy (NIRS). We recruited 75 individuals with MDD (36 females; mean age=39.23±12.49). They completed the Hamilton Rating Scale for Depression, Automatic Thoughts Questionnaire-Revised, Japanese version of the National Adult Reading Test, and the State-Trait Anxiety Inventory. Brain activation was measured by 52-channel NIRS. We found that activation in the vicinity of the right superior temporal gyrus is related to a deviation to negative of the proportion of positive and negative thoughts in individuals with MDD. Left dorsolateral prefrontal cortex activity was higher in the group with comparatively frequent positive thought. Our participants were patients taking antidepressant medication, which is known to influence brain activity. Second, the poor spatial resolution of NIRS increases the difficulty of identifying the measurement position. We found that activation of the prefrontal and temporal cortices is related to the proportion of automatic thoughts in the cognitive model of depression.
    Journal of affective disorders 07/2013; · 3.76 Impact Factor
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    ABSTRACT: The voxel-based morphometry (VBM) technique using brain magnetic resonance imaging (MRI) objectively maps gray matter loss on a voxel-by-voxel basis after anatomic standardization. In patients with Alzheimer's disease (AD), reductions of gray matter volume, mainly in the medial temporal structures, have been reported; however, inhomogeneity and geometric distortion of the field intensity hampers the reproducibility of MRI. In the present study, we developed a novel computed tomography (CT)-based VBM method and used this technique to detect volume loss in AD patients as compared with normal controls. The results were compared with MRI-based VBM using the same subjects. Pittsburgh Compound B ((11)C-PIB) positron emission tomography (PET)/CT was performed and two experts in neuro-nuclear medicine judged whether regional amyloid β load was consistent with a diagnosis of AD. Before the injection of (11)C-PIB, high-quality CT scans were obtained using the same PET/CT equipment. MRI was performed within a mean interval of 25.1 ± 8.2 days before the PET/CT scan. Using statistical parametric mapping 8 (SPM8), the extracted gray matter images from CT and MRI were spatially normalized using a gray matter template and smoothed using a Gaussian kernel. Group comparisons were performed using SPM8 between five (11)C-PIB-positive patients with probable AD and seven (11)C-PIB-negative age-matched controls with normal cognition. Gray matter volumes in the bilateral medial temporal areas were reduced in the AD group as compared with the cognitively normal group in both CT-based VBM (in the left; P < 0.0001, cluster size 2776 and in the right; P < 0.0001, cluster size 630) and MRI-based VBM (in the left; P < 0.0001, cluster size 381 and in the right, P < 0.0001, cluster size 421). This newly developed CT-based VBM technique can detect significant atrophy in the entorhinal cortex in probable AD patients as previously reported using MRI-based VBM. However, CT-VBM was more sensitive and revealed larger areas of significant atrophy than MR-VBM.
    Brain and behavior. 07/2013; 3(4):487-93.
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    ABSTRACT: Objectives Kir4.1, an inwardly rectifying potassium channel expressed on perivascular and perisynaptic end-feet of astrocytes, plays a pivotal role in the spatial buffering of the potassium in the brain. A recent study showed that autoantibodies directed to Kir4.1 are detectable in the serum derived from approximately half of the patients with multiple sclerosis (MS) and clinically isolated syndrome, although their pathogenic roles should be elucidated. Methods We studied Kir4.1 expression in MS and control brains by immunohistochemistry. ResultsWe found that reactive astrocytes expressed an intense immunoreactivity for Kir4.1 in active demyelinating lesions of MS, active lesion edges of neuromyelitis optica, ischemic lesion edges of cerebral infarction and neurodegenerative lesions of Alzheimer's disease. Reactive astrocytes accumulated in active MS lesions coexpressed Kir4.1 and AQP4. A subset of amyloid plaques in Alzheimer's disease brains also expressed Kir4.1. In contrast, infiltrating macrophages, activated microglia and surviving oligodendrocytes in active MS lesions did not express Kir4.1. Furthermore, cultured human astrocytes expressed Kir4.1, and the expression levels were not altered by exposure to tumor necrosis factor-α or interleukin-1β, but were elevated by transforming growth factor-β1. Conclusions These results show that reactive astrocytes abundantly express Kir4.1, and Kir4.1 immunoreactivity is not lost in active demyelinating lesions of MS.
    Clinical and Experimental Neuroimmunology. 06/2013; 4(1).
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    ABSTRACT: AIMS: Ubiquilin-1 acts as an adaptor protein that mediates the translocation of polyubiquitinated proteins to the proteasome for degradation. Although previous studies suggested a key role of ubiquilin-1 in the pathogenesis of Alzheimer's disease (AD), a direct relationship between ubiquilin-1 and Hirano bodies in AD brains remains unknown. METHODS: By immunohistochemistry, we studied ubiquilin-1 and ubiquilin-2 expression in the frontal cortex and the hippocampus of 6 AD and 13 control cases. RESULTS: Numerous Hirano bodies, accumulated in the hippocampal CA1 region of AD brains, expressed intense immunoreactivity for ubiquilin-1. They were much less frequently found in control brains. However, Hirano bodies did not express a panel of markers for proteasome, autophagosome, or pathogenic proteins, such as ubiquilin-2, ubiquitin, p62, LC3, beclin-1, HDAC6, PHF-tau, PDI, and phosphorylated TDP-43, but some of them expressed C9orf72. Ubiquilin-1-immunoreactive deposits were classified into four distinct morphologies, such as rod-shaped structures characteristic of Hirano bodies, dystrophic neurites contacting senile plaques, fragmented structures accumulated in the lesions affected with severe neuronal loss, and thread-shaped structures located mainly in the molecular layer of the hippocampus. CONCLUSIONS: Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in AD brains, suggesting that aberrant expression of ubiquilin-1 serves as one of pathological hallmarks of AD.
    Neuropathology and Applied Neurobiology 02/2013; · 4.84 Impact Factor
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    ABSTRACT: Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded.
    Journal of Psychiatric Research 01/2013; · 4.09 Impact Factor
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    ABSTRACT: OBJECTIVE: To cross-sectionally compare the regional white matter fractional anisotropy (FA) of cognitively normal (CN) older individuals and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD), separately focusing on the normal-appearing white matter (NAWM) and white matter hyperintensities (WMH), and to test the independent effects of presumed degenerative and vascular process on FA differences.$backslash$n$backslash$nMETHODS: Forty-seven patients with AD, 73 patients with MCI, and 95 CN subjects received diffusion tensor imaging and vascular risk evaluation. To properly control normal regional variability of FA, we divided cerebral white matter into 4 strata as measured from a series of young healthy individuals (H1 = highest; H2 = intermediate high; H3 = intermediate low; H4 = lowest anisotropy stratum).$backslash$n$backslash$nRESULTS: For overall cerebral white matter, patients with AD had significantly lower FA than CN individuals or patients with MCI in the regions with higher baseline anisotropy (H1, H2, and H3), corresponding to long corticocortical association fibers, but not in H4, which mostly includes heterogeneously oriented fibers. Vascular risk showed significant independent effects on FA in all strata except H1, which corresponds to the genu and splenium of the corpus callosum. Similar results were found within NAWM. FA in WMH was significantly lower than NAWM across all strata but was not associated with diagnosis or vascular risk.$backslash$n$backslash$nCONCLUSIONS: Both vascular and Alzheimer disease degenerative process contribute to microstructural injury of cerebral white matter across the spectrum of cognitive ability and have different region-specific injury patterns.
    Neurobiology of aging 01/2013; 27:101-107. · 5.94 Impact Factor
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    ABSTRACT: INTRODUCTION: Chromosome 9 open reading frame 72 (C9orf72) is an evolutionarily conserved protein with unknown function, expressed at high levels in the brain. An expanded hexanucleotide GGGGCC repeat located in the first intron of the C9orf72 gene represents the most common genetic cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Previous studies by immunohistochemistry with two different anti-C9orf72 antibodies named sc-138763 and HPA023873 showed that C9orf72 is expressed chiefly in the cytoplasm of neurons, and concentrated in the synaptic terminals in the brains of FTD/ALS with or without C9orf72 repeat expansion as well as those of the controls. At present, a pathological role of C9orf72 in the process of neurodegeneration remains unknown. METHODS: By immunohistochemistry, we studied C9orf72 expression in the frontal cortex and the hippocampus of 6 Alzheimer's disease (AD) and 13 control cases, including ALS, Parkinson's disease, multiple system atrophy, and non-neurological cases. RESULTS: The HPA023873 antibody showed a cross reactivity to GFAP, and therefore stained intensely reactive astrocytes in AD and non-AD brains. Both sc-138763 and HPA023873 antibodies labeled the neuronal cytoplasm and the neuropil with variable intensities, and intensely stained a cluster of p62-negative, UBQLN1-positive swollen neurites, which were distributed in the CA1 region and the molecular layer in the hippocampus of both AD and non-AD brains. Most notably, both of these antibodies reacted strongly with dystrophic neurites accumulated on senile plaques in AD brains. CONCLUSIONS: These results suggest a general role of C9orf72 in the process of neurodegeneration in a range of human neurodegenerative diseases.
    Alzheimer's Research and Therapy 08/2012; 4(4):33. · 4.39 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) research has largely concentrated on the study of cognitive decline, but the associated behavioral and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. Apathy is the most common neuropsychiatric manifestation in AD. Clinical, multimodal neuroimaging studies and pathologic studies of apathy in AD have suggested an association with frontal dysfunction but without a definitive localization. In this study, we examined the association between apathy and white matter integrity using diffusion tensor imaging (DTI). Twenty-one AD patients underwent DTI and neuropsychiatric and cognitive assessments. All fractional anisotropy (FA) maps were normalized to the standard space, and the association between the apathy scale and DTI metrics were evaluated voxel basically. Statistical parametric mapping analysis showed that there were statistically negative correlations between the apathy scale and FA values in the right anterior cingulate, right thalamus, and bilateral parietal regions using age, Mini-Mental State Examination score and sex as nuisance variables. Apathy in AD is associated with impaired white matter integrity in the anterior cingulate and medial thalamus. These results reinforce the confluence of evidence from other investigational modalities in implicating limbic dysfunction and related neuronal circuits in the neurobiology of apathy in AD.
    International Journal of Geriatric Psychiatry 07/2012; 27(7):722-6. · 2.98 Impact Factor
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    ABSTRACT: Accumulating evidence indicates that oxytocin plays an important role in social interactions. Previous studies also suggest altered oxytocin function in patients with schizophrenia and depression. However, few studies have examined the central oxytocin levels in these disorders. Cerebrospinal fluid (CSF) oxytocin levels were measured by ELISA in male participants consisting of 27 patients with schizophrenia, 17 with major depressive disorder (MDD), and 21 healthy controls. CSF oxytocin levels of patients with schizophrenia or MDD did not differ significantly with healthy controls. The antidepressant dose or the Hamilton depression rating scale score did not significantly correlate with the oxytocin levels in MDD patients. CSF oxytocin levels in schizophrenic patients significantly negatively correlated with second generation antipsychotic dose (r=-0.49, P=0.010) but not with first generation antipsychotic dose (r=-0.13, P=0.50). A significant correlation was observed between oxytocin levels and negative subscale of PANSS (r=-0.38, P=0.050). This correlation remained significant even after controlling for second generation antipsychotic dose (r=-0.47, P=0.016). We obtained no evidence of altered CSF oxytocin levels in patients with schizophrenia or those with MDD. However, lower oxytocin levels may be related to higher second generation antipsychotic dose and more severe negative symptoms in schizophrenia.
    Schizophrenia Research 06/2012; 139(1-3):201-6. · 4.59 Impact Factor
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    ABSTRACT: Aims: RGMa is a repulsive guidance molecule that induces the collapse of axonal growth cones by interacting with the receptor neogenin in the central nervous system (CNS) during development. It remains unknown whether RGMa plays a role in the neurodegenerative process of Alzheimer's disease (AD). We hypothesize that RGMa, if it is concentrated on amyloid plaques, might contribute to a regenerative failure of degenerating axons in AD brains. Methods: By immunohistochemistry, we studied RGMa and neogenin (NEO1) expression in the frontal cortex and the hippocampus of 6 AD and 12 control cases. The levels of RGMa expression were determined by qRT-PCR and western blot in cultured human astrocytes (AS) following exposure to cytokines and amyloid-beta (Aβ) peptides. Results: In AD brains, an intense RGMa immunoreactivity was identified on amyloid plaques and in the glial scar. In the control brains, the glial scar and vascular foot processes of astrocytes expressed RGMa immunoreactivity, while oligodendrocytes and microglia were negative for RGMa. In AD brains, a small subset of amyloid plaques expressed a weak NEO1 immunoreactivity, while some reactive astrocytes in both AD and control brains showed an intense NEO1 immunoreactivity. In AS, TGFβ(1) , Aβ(1-40) or Aβ(1-42) markedly elevated the levels of RGMa, and TGFβ(1) also increased its own levels. Coimmunoprecipitation analysis validated the molecular interaction between RGMa and the C-terminal fragment β of amyloid-beta precursor protein (APP). Furthermore, recombinant RGMa protein interacted with amyloid plaques in situ. Conclusions: RGMa, produced by TGFβ-activated astrocytes and accumulated in amyloid plaques and the glial scar, could contribute to the regenerative failure of degenerating axons in AD brains. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.
    Neuropathology and Applied Neurobiology 05/2012; · 4.84 Impact Factor
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    ABSTRACT: We examined histopathological changes in cerebrovascular amyloid deposition in a patient with cerebral amyloid angiopathy receiving corticosteroid therapy. A 69-year-old female developed subacute onset cognitive decline, and magnetic resonance image (MRI) showed subarachnoid hemorrhage with leptomeningeal enhancement. She entered in an apathetic state due to communicating hydrocephalus and a ventricle-peritoneal (V-P) shunt operation was performed. Brain biopsy disclosed multiple cortical microhemorrhages and severe Congophilic angiopathy with positive Aβ-immunoreactivity in most vessels. Inflammatory mononuclear cells surrounded a few severe amyloid-laden leptomeningeal vessels. She received high-dose corticosteroid, which was slowly tapered. She gradually recovered but finally died 1.5 years later with no recurrence of CAA-related hemorrhages. Postmortem examination of the brain showed multiple old microhemorrhages in the cortex and extensive degeneration of cerebral white matter. The cortical and leptomeningeal vascular walls showed a few Congophilic amyloid deposits, but small deposits with Aβ-immunoreactivity were frequently seen. There was no infiltration of inflammatory cells in either leptomeninges or vascular walls. Electron microscopy revealed sparse aggregation of amyloid fibrils in significant numbers of vascular walls. Biochemical analysis disclosed that Aβ1-40-immunoreactive amyloid protein fractions obtained from the patient's leptomeninges were very small in amount. Comparing the previous biopsy findings with those at autopsy, the total disappearance of the inflammatory cell infiltration and diminishing of the cerebrovascular amyloid deposits were noted.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 03/2012; 19(1):47-52. · 2.51 Impact Factor
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    ABSTRACT: Recent genetic association studies have identified the A-allele of rs1006737 within CACNA1C as a risk factor for schizophrenia as well as mood disorders. Some evidence suggests that this polymorphism plays a role in cognitive function both in schizophrenia patients and healthy individuals; however, the precise nature of this association remains unclear. Here we investigated the possible association of this polymorphism with a wide range of neurocognitive functions in schizophrenia patients and in healthy subjects. Schizophrenia patients exhibited significantly poorer performance on all the cognitive domains as compared to healthy controls. In patients, A-allele carriers demonstrated significantly worse logical memory performance than the G-allele homozygotes. In controls, no significant association was observed between the genotype and any of the cognitive domains examined. These results add to the literature suggesting that rs1006737 may be associated with schizophrenia through its detrimental effect on endophenotypic traits.
    Scientific Reports 01/2012; 2:634. · 5.08 Impact Factor

Publication Stats

2k Citations
519.69 Total Impact Points

Institutions

  • 1990–2014
    • National Center of Neurology and Psychiatry
      • • Department of Mental Disorder Research
      • • Department of Immunology
      Кодаиры, Tōkyō, Japan
  • 2006–2013
    • Meiji Pharmaceutical University
      Edo, Tōkyō, Japan
  • 2010
    • Okaya Municipal Hospital
      Hirano, Nagano, Japan