九州大学 研究者情報
研究者情報 (研究者の方へ)入力に際してお困りですか?
基本情報 研究活動 教育活動 社会活動 病院臨床活動
本田 裕之(ほんだ ひろゆき) データ更新日:2020.07.08

准教授 /  医学研究院 基礎医学部門 病態制御学


主な研究テーマ
認知症の臨床病理と病態解明
キーワード:認知症、アルツハイマ-病、レビ-小体型痴呆
2011.10~2023.03.
プリオン病の臨床病理と病態解明
キーワード:プリオン病、神経病理、Creutzfeldt-Jakob病
2011.10~2023.03.
ALSにおける臨床病理と病態解明
キーワード:筋萎縮性側索硬化症、TDP-43
2013.05~2023.03.
従事しているプロジェクト研究
各種プリオン病の全身臓器における異常プリオン蛋白検出と意義
2017.04~2020.03, 代表者:本田裕之, 九州大学医学部神経病理
本研究の目的は、ヒトプリオン病患者の全身臓器における、異常プリオン蛋白の蓄積部位や重合状態(オリゴマー)、感染性を明らかにする事である。近年、脳内のみならず末梢神経や全身臓器においても異常プリオン蛋白が検出され、その感染の危険性や病原性が問題視されている。急務の課題であるが、その詳細な検討は未だなされていない。当施設は、プリオン病患者においても全身解剖を従来基本としており、脳だけでなく多くの全身臓器の蓄積がある。プリオン蛋白はオリゴマーの状態で最も強い感染性と神経毒性を持つ。我々は、ゲル濾過法を用いたプリオン蛋白オリゴマー解析法を確立しており、その評価が可能である。併せて、近年確立された高感度検出法(PMCA法、QuIC法)や培養神経胞株を用いて、感染性や神経毒性の解析を行う。.
研究業績
主要原著論文
1. Sadashima S, Honda H, Suzuki SO, Shijo M, Aishima S, Kai K, Kira J, Iwaki T, Accumulation of Astrocytic Aquaporin 4 and Aquaporin 1 in Prion Protein Plaques., Journal of neuropathology and experimental neurology , 2020.04.
2. Hideomi Hamasaki, Hiroyuki Honda, Satoshi O. Suzuki, Masahiro Shijo, Tomoyuki Ohara, Yozo Hatabe, Tsuyoshi Okamoto, Toshiharu Ninomiya, Toru Iwaki, Tauopathy in basal ganglia involvement is exacerbated in a subset of patients with Alzheimer's disease
The Hisayama study, Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 10.1016/j.dadm.2019.04.008, 11, 415-423, 2019.12, [URL], Introduction: We have conducted the pathological cohort study of autopsied cases of Hisayama residents to reveal a recent trend of dementia-related pathology. We noticed a trend of putaminal involvement of Alzheimer's disease (AD) with parkinsonism. Then, we investigated the accurate prevalence of neurological diseases with putaminal AD pathology in the general population. Methods: We examined a series of 291 autopsies in the Hisayama study and performed image analysis of immunohistochemistry for microtubule-associated protein tau (MAPT) and amyloid β. Results: Approximately 65.6% and 36.1% of cases showed putaminal MAPT and amyloid deposits, respectively. Diffuse deposits of them were mainly found in the AD cases. Putaminal MAPT was highly associated with AD-related pathological criteria. Four of 22 cases with severe putaminal MAPT deposition were documented as having developed parkinsonism. Discussion: Severe MAPT accumulation in the basal ganglia was closely related to the development of AD pathology and could occur most frequently in AD cases without comorbidities..
3. Shinichiro Mori, Hiroyuki Honda, Takashi Ishii, Motoi Yoshimura, Naokazu Sasagasako, Satoshi O. Suzuki, Takayuki Taniwaki, Toru Iwaki, Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease, Neuropathology, 10.1111/neup.12600, 39, 5, 358-367, 2019.10, [URL], Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2-positive nuclear inclusions in all examined cases. Localization of poly (rC)-binding protein 1 (PCBP1) in 1C2-positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2-positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS-related familial amyotrophic lateral sclerosis..
4. Hiroyuki Honda, Masaki Matsumoto, Masahiro Shijo, Hideomi Hamasaki, Shoko Sadashima, Satoshi O. Suzuki, Shinichi Aishima, Keita Kai, Keiichi I. Nakayama, Naokazu Sasagasako, Toru Iwaki, Frequent Detection of Pituitary-Derived PrPres in Human Prion Diseases, Journal of neuropathology and experimental neurology, 10.1093/jnen/nlz075, 78, 10, 922-929, 2019.10, [URL], Human prion diseases including sporadic Creutzfeldt-Jakob disease (sCJD), inherited prion diseases, and acquired human prion diseases are lethal neurodegenerative diseases. One of the major sources of iatrogenic Creutzfeldt-Jakob disease was human growth hormone (hGH-iCJD) derived from contaminated cadaveric pituitaries. The incidence of hGH-iCJD has decreased since changing from growth hormone extracted from human cadaveric pituitaries to recombinant pituitary hormones. However, extensive analysis on the localization and detecting of abnormal prion protein in the pituitary gland are limited. In this study, we examined 9 autopsied brains and pituitary glands from 6 patients with prion disease (3 Gerstmann-Sträussler-Scheinker disease, 2 sCJD, and 1 dura mater graft-associated CJD) and 3 individuals with nonprion diseases. Western blot analysis of pituitary samples demonstrated unique glycoforms of normal cellular prion protein with molecular weights of 30-40 kDa, which was higher than the typical 25-35 kDa prion protein in brains. Proteomic analysis also revealed prion protein approximately the molecular weight of 40 kDa in pituitary samples. Moreover, proteinase K-resistant Prion protein was frequently detected in pituitary samples of the prion diseases. Immunohistochemistry for Prion protein revealed mosaic cellular distribution preferentially in growth hormone- or prolactin-producing cells..
5. Masahiro Shijo, Hideomi Hamasaki, Hiroyuki Honda, Satoshi O. Suzuki, Masaki Tachibana, Tetsuro Ago, Takanari Kitazono, Koji Iihara, Toru Iwaki, Upregulation of Annexin A1 in Reactive Astrocytes and Its Subtle Induction in Microglia at the Boundaries of Human Brain Infarcts, Journal of neuropathology and experimental neurology, 10.1093/jnen/nlz079, 78, 10, 961-970, 2019.10, [URL], Annexin A1 (ANXA1) has multiple functions, including anti-inflammatory effects, and is thought to be neuroprotective in various pathophysiologies of the central nervous system. The importance of ANXA1 in microglia and endothelial cells in ischemic environments in the brain has been recognized, but its detailed behavior in astrocytes in the ischemic brain remains unknown. Using immunohistochemistry, we therefore assessed the altered distribution of ANXA1 in human brain infarcts using 14 autopsied samples and 18 surgical samples. Elevated expression of ANXA1 was observed in reactive astrocytes in peri-infarct regions. ANXA1 accumulated at the cell periphery and in swollen cytoplasmic processes of reactive astrocytes, as well as at the rim of vacuoles at the boundary of necrosis, and colocalized with aberrantly distributed aquaporin 4 and excitatory amino acid transporter 1. Foamy macrophages in the necrotic core also expressed abundant ANXA1, whereas resident microglia at the boundary of necrosis rarely showed intrinsic expression of ANXA1. This characteristic distribution of ANXA1 in human brain infarcts may represent the good adaptability of reactive astrocytes to ischemic damage..
6. Fujii T, Takase KI, Honda H, Kawamura N, Yamasaki R, Urata M, Uchiumi T, Iwaki T, Kira JI, A case of toxic myopathy with multiple deletions in mitochondrial DNA associated with long-term use of oral anti-viral drugs for hepatitis B, Neuropathology, 2019.04.
7. Takayuki Fujii, Kei ichiro Takase, Hiroyuki Honda, Nobutoshi Kawamura, Ryo Yamasaki, Michiyo Urata, Takeshi Uchiumi, Toru Iwaki, Jun ichi Kira, Toxic myopathy with multiple deletions in mitochondrial DNA associated with long-term use of oral anti-viral drugs for hepatitis B
A case study, Neuropathology, 10.1111/neup.12548, 39, 2, 162-167, 2019.04, [URL], Oral nucleoside analogs (NAs) reduce hepatitis B virus (HBV) replication by inhibiting HBV DNA polymerase. However, NAs can also affect human mitochondrial DNA (mtDNA) polymerase, which can lead to mtDNA depletion (quantitative abnormality). Indeed, several mitochondrial myopathy cases have been reported in which a reduced mtDNA copy number was induced by oral NAs for hepatitis B. Herein, we report a case of toxic myopathy with multiple mtDNA deletions (qualitative abnormality) associated with long-term use of NAs for hepatitis B. A 68-year-old woman, who underwent long-term treatment with lamivudine and adefovir for chronic hepatitis B, developed proximal muscle weakness in the four extremities. Neurological examination showed mild proximal muscle weakness and atrophy in the four extremities. Upon admission to our hospital, her blood lactate/pyruvate ratio during an aerobic exercise test was elevated. Myogenic patterns were observed in lower limb muscles on electromyographic examination. Muscle magnetic resonance imaging revealed diffuse atrophy of proximal muscles in the four extremities with no signal changes. A biopsy from the biceps brachii muscle showed an abnormally large variation in fiber size, scattered muscle fibers with decreased cytochrome c oxidase activity, and ragged-red fibers. Analysis of mtDNA from skeletal muscle revealed no decrease in copy number but increased incidence of multiple deletions, including a deletion of 4977 base pairs (known as the common deletion) reflecting oxidative stress-induced mtDNA damage. This case study indicates that long-term oral antiviral therapy for hepatitis B can induce chronic oxidative damage to mtDNA resulting in qualitative mtDNA abnormalities and toxic myopathy..
8. Takayuki Fujii, Hiroyuki Honda, Ryo Yamasaki, Toru Iwaki, Jun Ichi Kira, Multiple mtDNA deletions due to mitochondrion toxicity of anti-hepadnaviral drugs
Comments to the letter from J. Finsterer, Neuropathology, 10.1111/neup.12563, 39, 4, 326-327, 2019.01, [URL].
9. Chang Shen, Hiroyuki Honda, Satoshi Suzuki, Norihisa Maeda, Masahiro Shijo, Hideomi Hamasaki, Naokazu Sasagasako, Naoki Fujii, Toru Iwaki, Dynactin is involved in Lewy body pathology, Neuropathology, 10.1111/neup.12512, 38, 6, 583-590, 2018.12, [URL], Dynactin forms a protein complex with dynein that retrogradely transports cargo along microtubules. Dysfunction of this dynein-dynactin complex causes several neurodegenerative diseases such as Perry syndrome, motor neuron diseases and progressive supranuclear palsy. Recently, we reported colocalization of phosphorylated α-synuclein (p-SNCA) and the largest subunit of dynactin (DCTN1) in Lewy body (LB)-like structures in Perry syndrome. Previous reports have not focused on the relationship between dynactin and synucleinopathies. Thus, we examined autopsied human brains from patients with Parkinson's disease, dementia with LBs, and multiple system atrophy using immunohistochemistry for p-SNCA, DCTN1, dynactin 2 (DCTN2, dynamitin) and dynein cytoplasmic 1 intermediate chain 1 (DYNC1I1). We also examined microtubule affinity-regulating kinases (MARKs), which phosphorylate microtubule-associated proteins and trigger microtubule disruption. Both brainstem-type and cortical LBs were immunopositive for DCTN1, DCTN2, DYNC1I1 and p-MARK and their staining often overlapped with p-SNCA. Lewy neurites were also immunopositive for DCTN1, DCTN2 and DYNC1I1. However, p-SNCA-positive inclusions of multiple system atrophy, which included both glial and neuronal cytoplasmic inclusions, were immunonegative for DCTN1, DCTN2, DYNC1I1 and p-MARK. Thus, immunohistochemistry for dynein-dynactin complex molecules, especially DCTN1, can clearly distinguish LBs from neuronal cytoplasmic inclusions. Our results suggest that dynactin is closely associated with LB pathology..
10. Norihisa Maeda, Hiroyuki Honda, Satoshi Suzuki, Naoki Fujii, Jun-Ichi Kira, Toru Iwaki, Mitochondrial dysfunction and altered ribostasis in hippocampal neurons with cytoplasmic inclusions of multiple system atrophy, Neuropathology, 10.1111/neup.12482, 38, 4, 361-371, 2018.08, [URL], Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disease. It has recently been shown that patients with MSA accompanied by cognitive decline display numerous neuronal cytoplasmic inclusions (NCIs) in the limbic neurons. We examined potential mechanisms underlying the formation of these NCIs by determining of mitochondrial function and statuses of RNA processing by analyzing 12 pathologically confirmed cases of MSA. Among them, four had cognitive impairment Semiquantitative evaluation using immunohistochemistry analyses revealed a significantly greater NCI burden in the hippocampal cornu ammonis 1 (CA1) subfield, subiculum, and amygdala in the cases with cognitive impairments compared with those without cognitive impairment. Immunofluorescent staining revealed that limbic neurons with NCIs often accelerated production of reactive oxygen species (ROS) and degraded mitochondrial quality control. Immunofluorescent staining also revealed that neurons with these NCIs translocated heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) from the nucleus and aggregated abnormally at the perinuclear rim. Since the NCIs in the hippocampal neurons of MSA with cognitive impairments were more numerous, the neuronal mitochondrial dysfunction and altered ribostasis observed in NCI formation may be involved in the hippocampal degeneration of MSA..
11. Hiroyuki Honda, Naokazu Sasagasako, Chang Shen, Masahiro Shijo, Hideomi Hamasaki, Satoshi Suzuki, Yoshio Tsuboi, Naoki Fujii, Toru Iwaki, DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy, Parkinsonism and Related Disorders, 10.1016/j.parkreldis.2018.02.038, 51, 105-110, 2018.06, [URL], Introduction: Perry syndrome is a rapidly progressive, autosomal dominant parkinsonism characterized by central hypoventilation, depression and severe weight loss. To date, eight DCTN1 mutations have been identified associated with Perry syndrome. A novel F52L DCTN1 mutation case of Perry syndrome is characterized by late-onset parkinsonism and frontotemporal atrophy. Methods: A Japanese woman suffered from slowly progressing parkinsonism since age 48. At age 59, she developed central hypoventilation, and required breathing assistance. Gene analysis identified a p.F52L mutation in DCTN1 and she was diagnosed with Perry syndrome. She died of aspiration pneumonia at age 74. Results: Postmortem examination revealed severe neuronal loss in the substantia nigra and the putamen. Immunohistochemistry for DCTN1 revealed many abnormal aggregates, mainly in neurons in the brainstem and basal ganglia. Additionally, numerous abnormal phosphorylated tau deposits including neurofibrillary tangles, tuft-shaped astrocytes and coiled bodies were observed mainly in the basal ganglia, brainstem and cerebellum. These correspond with the neuropathologic criteria for progressive supranuclear palsy. Colocalization of DCTN1 and tau were occasionally seen. Colocalization of phosphorylated α-synuclein and DCTN1 were also observed in Lewy body-like structures in oculomotor nuclei. Phosphorylated TARDBP-positive neuronal cytoplasmic inclusions were few. Conclusion: In conjunction with long disease duration and aging, our findings suggest that the F52L DCTN1 mutation may evoke severe tauopathy and moderate α-synucleinopathy..
12. Masahiro Shijo, Hiroyuki Honda, Satoshi Suzuki, Hideomi Hamasaki, Masaaki Hokama, Nona Abolhassani, Yusaku Nakabeppu, Toshiharu Ninomiya, Takanari Kitazono, Toru Iwaki, Association of adipocyte enhancer-binding protein 1 with Alzheimer's disease pathology in human hippocampi, Brain Pathology, 10.1111/bpa.12475, 28, 1, 58-71, 2018.01, [URL], Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes. Up-regulation of AEBP1 in the hippocampi of patients with Alzheimer's disease (AD) has been revealed by microarray analyses of autopsied brains from the Japanese general population (the Hisayama study). In this study, we compared the expression patterns of AEBP1 in normal and AD brains, including in the hippocampus, using immunohistochemistry. The subjects were 24 AD cases and 52 non-AD cases. Brain specimens were immunostained with antibodies against AEBP1, tau protein, amyloid β protein, NF-κB, GFAP and Iba-1. In normal brains, AEBP1 immunoreactivity mainly localized to the perikarya of hippocampal pyramidal neurons, and its expression was elevated in the pyramidal neurons and some astrocytes in AD hippocampi. Although AEBP1 immunoreactivity was almost absent in neurons containing neurofibrillary tangles, AEBP1 was highly expressed in neurons with pretangles and in the tau-immunopositive, dystrophic neurites of senile plaques. Nuclear localization of NF-κB was also observed in certain AEBP1-positive neurons in AD cases. Comparison of AD and non-AD cases suggested a positive correlation between the expression level of AEBP1 and the degree of amyloid β pathology. These findings imply that AEBP1 protein has a role in the progression of AD pathology..
13. Masahiro Shijo, Hiroyuki Honda, Sachiko Koyama, Koji Ishitsuka, Koichiro Maeda, Junya Kuroda, Mitsugu Tanii, Takanari Kitazono, Toru Iwaki, Dura mater graft-associated Creutzfeldt-Jakob disease with 30-year incubation period, Neuropathology, 10.1111/neup.12359, 37, 3, 275-281, 2017.06, [URL], Over 60% of all patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been diagnosed in Japan. The incubation period has ranged from 1 to 30 years and the age at onset from 15 to 80 years. Here, we report a 77-year-old male Japanese autopsied dCJD case with the longest incubation period so far in Japan. He received a cadaveric dural graft at the right cranial convexity following a craniotomy for meningioma at the age of 46. At 30 years post-dural graft placement, disorientation was observed as an initial symptom of dCJD. He rapidly began to present with inconsistent speech, cognitive impairment and tremor of the left upper extremity. Occasional myoclonic jerks were predominantly observed on the left side. Brain MRI presented hyperintense signals on diffusion-weighted and T2-weighted images, at the right cerebral cortex. The most hyperintense lesion was located at the right parietal lobe, where the dura mater graft had been transplanted. Single-photon emission CT scan showed markedly decreased cerebral blood flow at the right parietal lobe. EEG revealed diffuse and slow activities with periodic sharp-wave complex discharges seen in the right parietal, temporal and occipital lobes. He died of pneumonia 9 months after onset. Brain pathology revealed non-plaque-type dCJD. Laterality of neuropathological changes, including spongiform change, neuronal loss, gliosis or PrP deposits, was not evident. Western blot analysis showed type 1 PrPCJD. Alzheimer-type pathology and PSP-like pathology were also observed..
14. Hiroyuki Honda, Kensuke Sasaki, Hiroshi Takashima, Daisuke Mori, Sachiko Koyama, Satoshi Suzuki, Toru Iwaki, Different complicated brain pathologies in monozygotic twins with Gerstmann-Sträussler-Scheinker disease, Journal of Neuropathology and Experimental Neurology, 10.1093/jnen/nlx068, 76, 10, 854-863, 2017.01, [URL], Gerstmann-Sträussler-Scheinker disease (GSS) is an autosomal, dominantly inherited prion disease. In this study, we present different complicated brain pathologies determined postmortem of monozygotic GSS twin sisters. Case 1 showed cerebellar ataxia at the age of 58 years, and died at 66 years. Case 2 became symptomatic at the age of 75 years, and died at 79 years. There was a 17-year difference in the age of onset between the twins. Postmortem examination revealed numerous prion protein (PrP) plaques in the brains of both cases. The spongiform change and brain atrophy in case 1 were more severe compared with those in case 2. Western-blot analysis identified proteinase-resistant PrP (PrPres) at the molecular weight of 21-30 kDa and 8 kDa in the twins. Gel filtration revealed that PrPres was mainly composed of PrP oligomer. PrPres signal patterns were similar between the twins. Additionally, case 1 showed α-synucleinopathy and case 2 showed Alzheimer disease pathology. These different proteinopathies were involved in the amyloid plaque formations of both cases. The degree of GSS pathology was mainly related to disease duration. The amyloid plaque formations could be decorated by concomitant neuropathological changes such as a-synucleinopathy and tauopathy..
15. Hideomi Hamasaki, Hiroyuki Honda, Tsuyoshi Okamoto, Sachiko Koyama, Satoshi Suzuki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Toru Iwaki, Recent Increases in Hippocampal Tau Pathology in the Aging Japanese Population
The Hisayama Study, Journal of Alzheimer's Disease, 10.3233/JAD-160521, 55, 2, 613-624, 2017.01, [URL], Background: The Hisayama study is a prospective cohort study of lifestyle-related diseases that commenced in 1961. Through it, a significant increasing trend in the prevalence of Alzheimer's disease has been observed over the past 18 years. Objectives: We sought to investigate the increases in brain pathology related to Alzheimer's disease using automated MATLAB morphometric analyses for quantifying tau pathology. Methods: We examined a series of autopsied cases from Hisayama residents obtained between 1998 and 2003 (group A: 203 cases), and between 2009 and 2014 (group B: 232 cases). We developed custom software in MATLAB to analyze abnormal tau deposits quantitatively. Specimens were immunostained with both anti-amyloid-β-protein and anti-phosphorylated tau antibodies. Results: Both the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria for senile plaques and Braak stage for NFT were higher in group B. Morphometric analyses of the hippocampi also revealed a trend toward increased tau pathology in both men and women over 80 years of age in group B. The increases were also significant when the subjects were examined independently according to high or low CERAD scores and in all levels of AD neuropathologic change according to the National Institute on Aging-Alzheimer's Association guidelines (2012). Conclusion: We revealed a recent trend of increased tauopathy in the older people, which is partly independent of amyloid-β pathology..
16. Hiroyuki Honda, Kensuke Sasaki, Hideomi Hamasaki, Masahiro Shijo, Sachiko Koyama, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Satoshi Suzuki, Toru Iwaki, Trends in autopsy-verified dementia prevalence over 29 years of the Hisayama study, Neuropathology, 10.1111/neup.12298, 36, 4, 383-387, 2016.08, [URL], We investigated the trends in dementia over the past 29 years in the town of Hisayama, Japan using 1266 autopsy specimens. The Hisayama study is a prospective cohort study of lifestyle-related diseases that was started in 1961. Clinical examination of dementia was started in 1985 with five detailed cross-sectional assessments conducted in 1985, 1992, 1998, 2005 and 2012. To examine the trends in dementia, we divided the 1266 autopsy samples into five groups according to the year of death: I (1986–1991, 257 cases), II (1992–1997, 268 cases), III (1998–2004, 318 cases), IV (2005–2011, 296 cases) and V (2012–2014, 127 cases). The prevalence of all-cause dementia significantly increased over time (28.4% in group I, 22.4% in group II, 32.1% in group III, 30.1% in group IV, 51.2% in group V; P for trend <0.001). A similar trend was observed for Alzheimer's disease (AD) (15.2%, 11.9%, 17.3%, 20.6% and 33.1%, respectively; P for trend <0.001). A significant increasing trend was observed in both men and women. A rapid increase in senile dementia of the NFT type (SD-NFT) in recent years was notable. Vascular dementia was the most common type of dementia in men prior to 2004; however, its prevalence decreased over time. Our study revealed that tauopathies, including AD and SD-NFT, significantly increased in the aged Japanese population over the course of this study. The neuritic plaque pathology of AD was associated with metabolic disorders such as insulin resistance and abnormal lipid metabolism, whereas the risk factors for tau pathology remain unclear. Although aging is considered one of the important risk factors accelerating tau pathology, there could be other risk factors associated with lifestyle diseases..
17. K. Matsuzono, Hiroyuki Honda, K. Sato, R. Morihara, K. Deguchi, N. Hishikawa, T. Yamashita, S. Kono, Y. Ohta, Toru Iwaki, K. Abe, 'PrP systemic deposition disease'
Clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178, European Journal of Neurology, 10.1111/ene.12905, 23, 1, 196-200, 2016.01, [URL], Background and purpose: A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously. Methods: Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). Results: Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. Conclusion: The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology..
18. Hiroyuki Honda, Kosuke Matsuzono, Soichiro Fushimi, Kota Sato, Satoshi Suzuki, Koji Abe, Toru Iwaki, C-terminal-deleted prion protein fragment is a major accumulated component of systemic PrP deposits in hereditary prion disease with a 2-Bp (CT) deletion in PRNP codon 178, Journal of Neuropathology and Experimental Neurology, 10.1093/jnen/nlw077, 75, 11, 1008-1019, 2016.01, [URL], Prion protein (PrP) has 2 glycosylated sites and a glycosylphosphatidylinositol (GPI) anchor on the C-terminal. Reports on genetic prion disease with GPI anchorless PrP are very limited. In this study, we characterized the molecular alterations of mutated PrP in a 37-year-old female autopsy case with a recently identified PRNP mutation involving a 2-bp deletion in codon 178 that results in a premature stop codon mutation in codon 203. Postmortem examination revealed numerous irregularly shaped coarse PrP deposits and multicentric plaques in the brain that were mainly comprised of C-terminal deleted abnormal PrP primarily derived from the mutant allele. Additionally, abnormal PrP deposits were detected in almost all other examined organs. PrP was mainly deposited in peripheral nerves, smooth muscles, and blood vessels in non-CNS tissues. Western blot analysis after proteinase K treatment showed protease-resistant PrP (PrPres) signals with a molecular weight of 9 kDa; weak PrPres smear signals of 9 to 80 kDa were also noted. Gel filtration revealed that PrPres oligomers were mainly composed of the PrP fragments. In conclusion, the mutated PrP lacking that GPI anchor was truncated shortly and deposited in almost every examined organ..
19. Hiroyuki Honda, Hideomi Hamasaki, Tomihiro Wakamiya, Satoshi O Suzuki, Naoki Fujii, Toru Iwaki, Loss of hnRNPA1 in ALS spinal cord motor neurons with TDP-43-positive inclusions, Neuropathology, 10.1111/neup.12153, 35, 1, 37-43, 2015.01.
20. Masaaki Hokama, Sugako Oka, Julio Leon, Toshiharu Ninomiya, Hiroyuki Honda, Kensuke Sasaki, Toru Iwaki, Tomoyuki Ohara, Tomio Sasaki, Frank M. LaFerla, Yutaka Kiyohara, Yusaku Nakabeppu, Altered expression of diabetes-related genes in Alzheimer's disease brains
The Hisayama study, Cerebral Cortex, 10.1093/cercor/bht101, 24, 9, 2476-2488, 2014.01, [URL], Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM..
21. Hideomi Hamasaki, Hiroyuki Honda, Satoshi Suzuki, Masaaki Hokama, Yutaka Kiyohara, Yusaku Nakabeppu, Toru Iwaki, Down-regulation of MET in hippocampal neurons of Alzheimer's disease brains, Neuropathology, 10.1111/neup.12095, 34, 3, 284-290, 2014.01, [URL], We found that mRNA of MET, the receptor of hepatocyte growth factor (HGF), is significantly decreased in the hippocampus of Alzheimer's disease (AD) patients. Therefore, we tried to determine the cellular component-dependent changes of MET expressions. In this study, we examined cellular distribution of MET in the cerebral neocortices and hippocampi of 12 AD and 11 normal controls without brain diseases. In normal brains, MET immunoreactivity was observed in the neuronal perikarya and a subpopulation of astrocytes mainly in the subpial layer and white matter. In AD brains, we found marked decline of MET in hippocampal pyramidal neurons and granule cells of dentate gyrus. The decline was more obvious in the pyramidal neurons of the hippocampi than that in the neocortical neurons. In addition, we found strong MET immunostaining in reactive astrocytes, including those near senile plaques. Given the neurotrophic effects of the HGF/MET pathway, this decline may adversely affect neuronal survival in AD cases. Because it has been reported that HGF is also up-regulated around senile plaques, β-amyloid deposition might be associated with astrocytosis through the HGF signaling pathway..
22. Hiroyuki Honda, R. Ishii, A. Hamano, K. Itoh, Satoshi Suzuki, S. Fushiki, M. Nakagawa, Toru Iwaki, Microsphere formation in a subtype of Creutzfeldt-Jakob disease with a V180I mutation and codon 129 MM polymorphism, Neuropathology and Applied Neurobiology, 10.1111/nan.12047, 39, 7, 844-848, 2013.12, [URL].
23. Hiroyuki Honda, Kensuke Sasaki, Haruhiko Minaki, Kenta Masui, Satoshi Suzuki, Katsumi Doh-ura, Toru Iwaki, Protease-resistant PrP and PrP oligomers in the brain in human prion diseases after intraventricular pentosan polysulfate infusion, Neuropathology, 10.1111/j.1440-1789.2011.01245.x, 32, 2, 124-132, 2012.04, [URL], Intraventricular infusion of pentosan polysulfate (PPS) as a treatment for various human prion diseases has been applied in Japan. To evaluate the influence of PPS treatment we performed pathological examination and biochemical analyses of PrP molecules in autopsied brains treated with PPS (one case of sporadic Creutzfeldt-Jakob disease (sCJD, case 1), two cases of dura mater graft-associated CJD (dCJD, cases 2 and 4), and one case of Gerstmann-Sträussler-Scheinker disease (GSS, case 3). Six cases of sCJD without PPS treatment were examined for comparison. Protease-resistant PrP (PrPres) in the frontal lobe was evaluated by Western blotting after proteinase K digestion. Further, the degree of polymerization of PrP molecules was examined by the size-exclusion gel chromatography assay. PPS infusions were started 3-10 months after disease onset, but the treatment did not achieve any clinical improvements. Postmortem examinations of the treated cases revealed symmetrical brain lesions, including neuronal loss, spongiform change and gliosis. Noteworthy was GFAP in the cortical astrocytes reduced in all treated cases despite astrogliosis. Immunohistochemistry for PrP revealed abnormal synaptic deposits in all treated cases and further plaque-type PrP deposition in case 3 of GSS and case 4 of dCJD. Western blotting showed relatively low ratios of PrPres in case 2 of dCJD and case 3 of GSS, while in the treated sCJD (case 1), the ratio of PrPres was comparable with untreated cases. The indices of oligomeric PrP were reduced in one sCJD (case 1) and one dCJD (case 2). Although intraventricular PPS infusion might modify the accumulation of PrP oligomers in the brains of patients with prion diseases, the therapeutic effects are still uncertain..
24. Haruhiko Minaki, Kensuke Sasaki, Hiroyuki Honda, Toru Iwaki, Prion protein oligomers in Creutzfeldt-Jakob disease detected by gel-filtration centrifuge columns
Original Article, Neuropathology, 10.1111/j.1440-1789.2009.01007.x, 29, 5, 536-542, 2009.10, [URL], Prion diseases are diagnosed by the detection of accumulation of abnormal prion protein (PrP) using immunohistochemistry or the detection of protease-resistant abnormal PrP (PrPres). Although the abnormal PrP is neurotoxic by forming aggregates, recent studies suggest that the most infectious units are smaller than the amyloid fibrils. In the present study, we developed a simplified method by applying size-exclusion gel-filtration chromatography to examine PrP oligomers without proteinase K digestion in Creutzfeldt-Jakob disease (CJD) samples, and evaluated the correlation between disease severity and the polymerization degree of PrP. Brain homogenates of human CJD and non-CJD cases were applied to the gel-filtration spin columns, and fractionated PrP molecules in each fraction were detected by western blot. We observed that PrP oligomers could be detected by the simple gel-filtration method and distinctly separated from monomeric cellular PrP (PrPc). PrP oligomers were increased according to the disease severity, accompanied by the depletion of PrPc. The separated PrP oligomers were already protease-resistant in the case with short disease duration. In the cases with quite severe pathology the oligomeric PrP reached a plateau, which may indicate that PrP molecules could mostly develop into amyloid fibrils in the advanced stages. The increase of PrP oligomers correlated with the degree of histopathological changes such as spongiosis and gliosis. The decrease of monomeric PrPc was unexpectedly obvious in the diseased cases. Dynamic changes of both oligomerization of the human PrP and depletion of normal PrPc require further elucidation to develop a greater understanding of the pathogenesis of human prion diseases..
主要総説, 論評, 解説, 書評, 報告書等
1. 本田 裕之, 鈴木 諭, クロイツフェルト・ヤコブ病, 病理と臨床, 2015.04.
2. 本田 裕之, 岩城 徹, 病理学から見た認知症の原因疾患と疫学ー久山町研究からー, 最新医学, 2013.04, 日本人の認知症は65歳以上人口における約1割に達しており,顕著な増加傾向にある.久山町疫学研究では1985年から65歳以上の住民を対象に認知症調査を開始し,剖検による病理学的診断によって病型分類の精度を高めてきた.その結果,アルツハイマー病の増加が際立っていることが明らかとなった. 耐糖能異常がアルツハイマー病の老人斑の形成および発症の危険因子となり,その増加傾向に関与している..
主要学会発表等
1. 本田裕之、岩城徹, 脳内占拠生病変を有したAIDSの一剖検例, 第60回日本神経病理学会, 2019.07.
2. 濱崎英臣、本田裕之、岡本剛、二宮利治、鈴木諭、岩城徹, 連続剖検症例における被殻のtau・amyloid免疫組織化学染色の定量解析: 久山町研究, 第60回日本神経病理学会, 2019.07.
3. 本田 裕之、松本 雅紀、濱崎 英臣、鈴木 諭、相島 慎一、甲斐 敬太、中山 敬一、笹ケ迫 直一、岩城 徹, ヒトprion病における下垂体由来異常型prion蛋白の検出, 第60回日本神経病理学会, 2019.07.
4. Honda H, Hamasaki H, Okamoto T, Ninomiya T, Iwaki T, Trends in dementia prevalence over 31 years of the Hisayama study, International Congress of Neuropathology, 2018.07, Introduction: In Japan, dementia has become a serious social problem. The Hisayama study is a prospective cohort study of lifestyle-related diseases including dementia that was started in1961. In the population-based study, it has been reported that all-cause dementia and Alzheimer’s disease (AD) significantly increased in recent years.
Methods: The aim of this study is to clarify the trends in dementia using data from 1371 autopsied performed over the past 31 years (1986-2016). Throughout the whole period, the autopsy rate is about 75%. We divided the 1371 autopsy samples into five groups according to the year of death: I (1986–1991, 257 cases), II (1992–1997, 268 cases), III (1998–2004, 318 cases), IV (2005–2011, 296 cases), and V (2012–2016, 232 cases). In addition, we investigated the increases in brain pathology related to AD using automated morphometric analyses for quantifying tau pathology.
Results: The prevalence of all-cause and AD significantly increased. A significant increasing trend was observed in both men and women. A rapid increase in senile dementia of the NFT type (SD-NFT) in recent years was notable. The morphometric analyses revealed a significant increasing of tau pathology in recent years. The significance was also observed regardless of the senile plaques.
Conclusion: We revealed a recent trend of increased tauopathy such as AD and SD-NFT, which is partly independent of amyloid-β pathology. Although aging is considered one of the important risk factors accelerating tau pathology, there could be other risk factors associated with lifestyle diseases..
5. Honda H, Shen C, Suzuki O Satoshi, Sasagasako N, Iwaki T, Dynactin is involved in Lewy body pathology, International Congress of Neuropathology, 2018.07, Introduction: Dynactin forms a protein complex with dynein and the complex transports cargo retrogradely along microtubules. Dysfunction of the dynein-dynactin complex causes several neurodegenerative disorders, such as Perry syndrome. Recently, we reported colocalization of phosphorylated α-synuclein (p-SCNA) and the largest subunit of dynactin (DCTN1) in Lewy body-like structures in Perry syndrome. However, the relationship between dynactin and synucleinopathies has not been clarified. In this study, we examined the possible involvement of the dynein-dynactin complex in synucleinopathies such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).
Methods: We examined 13 autopsied human brains of patients with synucleinopathy (5 PD, 5 DLB and 3 MSA). Immunohistochemistry for p-SNCA, DCTN1 (dynactin) and DYNC1I1 (dynein) was performed. We also examined microtubule affinity regulating kinases (p-MARKs), which phosphorylate microtubule-associated proteins and trigger microtubule disruption. Double immunofluorescence was also performed.
Results: Both brainstem and cortical Lewy bodies were immunopositive for DCTN1, DYNC1I1 and p-MARK and their stainings often overlapped with p-SNCA. Lewy neurites were also immunopositive for DCTN1 and DYNC1I1. However, p-SNCA-positive inclusions of MSA such as glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were negative for DCTN1, DYNC1I1 and p-MARK.
Conclusion: Our results suggest that dynactin is closely associated with Lewy body pathology. In addition, immunohistochemistry for dynein-dynactin complex molecules, especially DCTN1, can distinguish Lewy bodies clearly from neuronal cytoplasmic inclusions of MSA..
6. 本田 裕之, 鈴木 諭, 岩城 徹, 進行性核上性麻痺に類似したタウオパチーを合併したPerry症候群 (DCTN1, F52L)の1剖検例, 第58回日本神経病理学会総会学術研究会, 2017.06.
7. 濱崎英臣, 本田 裕之, 鈴木 諭, 岩城 徹, 高齢者住民における海馬の異常tau蛋白蓄積増加に影響を与える神経病理所見, 第58回日本神経病理学会総会学術研究会, 2017.06.
8. 司城昌大, 本田 裕之, 鈴木 諭, 岩城 徹, 脳腱黄色腫症2剖検例の神経病理学的特徴, 第58回日本神経病理学会総会学術研究会, 2017.06.
9. 本田 裕之, 岩城 徹, PrP systemic deposition disease(D178fs25)における免疫組織化学的・蛋白化学的検討, 第37回日本神経病理学会総会学術研究会, 2016.06.
10. 本田 裕之, 岩城 徹, 一般住民における認知症病理の時代的変遷. 久山町研究 [シンポジウム], 第56回日本神経病理学会総会学術研究会, 2015.06.
11. 本田 裕之, 高島洋, 森大輔, 佐々木健介, 濱崎英臣, 吉村俊朗, 鈴木 諭, 岩城 徹, 発症に17年の差をみとめたGSS一卵性双生児姉妹例の病理学的検討, 日本神経病理学会総会学術研究会, 2014.06, [目的] 遺伝性プリオン病であるGSSは家系内浸透率が高い疾患であるが、その発症年齢や表現型は同一家系内においても多様性がある。我々はGSS (P102L)の一卵性双生児姉妹例で発症に17年の差がみられた剖検症例を経験したので、その病理像を報告する。
[症例] 症例1は一卵性双生児の姉で58歳時に歩行失調で発症した。62歳時に認知症がみられ68歳で死亡した。症例2は妹で、75歳時に歩行失調で発症した。77歳時に認知症がみられ79歳で死亡した。いずれも死後病理解剖された。
[病理所見] 症例1の脳重量は790gであり著明に萎縮していた。組織学的には、皮質の神経細胞脱落、海綿状変化やグリオーシスをみとめプリオン蛋白陽性のKuru斑を多くみとめた。α-synuclein陽性のLewy bodyを脳幹および辺縁系にみとめた。症例2の脳重量は1170gであり大脳や小脳の萎縮は軽度であった。組織学的にはプリオン蛋白陽性のKuru斑を多くみとめた。老人斑が多数みられ (CERAD: Frequent)リン酸化タウ蛋白の拡がりはBraak stage Vに相当し、病理学的にAlzheimer病の合併もみられた。Western blottingではいずれの症例も、type 1に相当するPrPresがみられ、更にGSSに特徴的とされる8kD付近のPrPresもみとめた。
[考察・結論] 症状の表現型やプリオン蛋白の沈着パターンは類似していたが発症年齢や罹病期間は異なっていた。またα-synucleinopathyやAD病理の有無などの相違点もみられた。プリオン蛋白遺伝子変異は、疾患の発症や表現型、プリオン蛋白の沈着パターンに強く関与していると思われた。一方で発症年齢や罹病期間においては、病理学的な相違点もあり何らかの非遺伝的な要素の関与も示唆された。
.
12. 本田 裕之, 石井亮太郎, 濱野愛, 伊東恭子, 中川正法, 伏木信次, 岩城 徹, プリオン蛋白陽性の小球状構造物を有するV180I CJDにおける免疫組織化学的・蛋白化学的検討, 日本神経病理学会総会学術研究会, 2013.04, 【はじめに】我々は特異なPrP陽性の小球状構造物microsphereを有するV180I CJDの1剖検例を昨年報告した。今回、免疫組織化学的・蛋白化学的に分析を行なった。【症例】70歳女性。死亡約6年前より地誌的障害が出現し、その後記憶障害を認めた。PrP遺伝子に180Val/Ile変異があり遺伝性CJDと診断された。4.3年前よりペントサンポリ硫酸脳室内持続注入を開始したが症状は徐々に進行し死亡した。【病理所見】PrP免疫染色(3F4)で、シナプス型沈着に加えて大きさが比較的均一で辺縁が整なmicrosphereを大脳皮質、海馬傍回、中脳、小脳皮質に多数認めた。他のエピトープを認識する抗PrP抗体でmicrosphereは8B4(N末)と8G8(100-107)にて陽性を示したが、8H4(C末)はmicrosphere、シナプス型沈着共に陽性所見が得られなかった。3F4、8G8および8H4を用いたwestern blottingでPK抵抗性の無糖鎖型と1糖鎖型のPrPresを認め、2糖鎖型のPrPresは認められなかった。遠心ゲル濾過法で分画したPrPオリゴマーでも上記と同様にPK処理後に2糖鎖型PrPが消失した。【考察】V180I CJDのwestern blottingでは2糖鎖型のPrPを欠いた2バンドが特徴的であることが知られているが、今回ゲル濾過法により得られたオリゴマー分画でもPK抵抗性の2糖鎖型はみられず、異常プリオン蛋白は大部分が変異アレル由来であることが示された。V180I CJDにみられた特異なmicrosphereは各種PrP抗体に陽性で、Congo red染色でアミロイドの性格を示しており、変異アレル由来の異常PrPから構成されている可能性が高い。
.
13. H. Honda, T. Okamoto, Y. Hamamoto, H. Hamasaki, S. O. Suzuki, T. Iwaki, Computational morphological analyses of abnormal tau deposits in human brains., Society for Neuroscience, 2012.10, Computational morphological analyses of abnormal tau deposits in human brains

H. Honda1, T. Okamoto2, Y. Hamamoto1, H. Hamasaki1, S. O. Suzuki1, T. Iwaki1

1Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
2 Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

Hyperphosphorylated tau deposits in brains are implicated in a wide variety of neurodegenerative diseases, called ''tauopathy''. Tau deposits are characterized by their locations and shapes in addition to individual tau protein isoform. By focusing on the morphology, they are commonly classified into five major structures: neurofibrillary tangles (NFTs), argyrophilic grains (AGs), neuropil threads (NTs), Pick bodies, and glial tauopathies. This classification is mainly based on a subjective assessment, and the morphological range of each structure has not been strictly defined. In order to propose classification criteria quantitatively for abnormal tau deposits, we analyzed tau images using unique programs for image processing. We performed immunohistochemical analysis using anti-hyperphosphorylated tau antibody (AT8) in autopsied brain tissues from six patients with tauopathy (Alzheimer’s disease, argyrophilic grain disease, senile dementia of the neurofibrillary tangles, Pick’s disease, progressive supranuclear palsy, and corticobasal degeneration). We developed image analyses programs in Matlab language. The program was divided into three parts. The first part extracted all tau positive structures from background in the digital photos with color-based segmentation using k-means clustering. The second part identified each tau structure and calculated its area and morphometric indices (e.g. roundness, eccentricity, and flattering). The last part classified tau structures using k-means clustering and performed statistical analyses. The area of structure easily distinguished NFTs from the others because the NFTs were obviously larger than the other structures. All indices calculated in our analyses failed to distinguish clearly between neuropil pathologies and glial tauopathies, whereas the morphometric indices showed disease-specific predominance of tau structures in the lesion. We developed new computer-assisted analyses for the quantitative evaluation of abnormal tau deposits.
H. Honda and T. Okamoto contributed equally to this work.
.
14. 本田裕之、石井亮太郎、伊東恭子、中川正法、伏木信次、岩城徹, V180I CJDの剖検例における特異なプリオン蛋白沈着パターン, 第53回日本神経病理学会総会学術研究会, 2012.06.
15. 本田裕之、佐々木健介、藤井直樹、鈴木諭、岩城徹, 情動障害を伴うALSにおけるtauopathyおよびTDP-43 proteinopathyの検討, 第51回日本神経病理学会総会学術研究会, 2010.04.
16. 本田裕之、佐々木健介、鈴木諭、岩城徹, ペントサンポリ硫酸治療症例におけるプリン蛋白重合度変化の解析, 第50回日本神経病理学会総会学術研究会, 2009.06.
17. 本田裕之、佐々木健介、鈴木諭、岩城徹, プリオン病の病理形態学的および蛋白生化学的定量解析の試み, 第49回日本神経病理学会総会学術研究会, 2008.05.
学会活動
所属学会名
日本神経病理学会
日本神経学会
日本内科学会
学会大会・会議・シンポジウム等における役割
2015.06.03~2015.06.05, 日本神経病理学会総会学術研究会, 座長(Chairmanship).
2014.06.05~2014.06.07, 日本神経病理学会総会学術研究会, 座長(Chairmanship).
2015.06.03~2015.06.05, 第56回日本神 経病理学会総会学術研究会, シンポジウム演者.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2018年度
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2017年度~2019年度, 基盤研究(C), 代表, 各種プリオン病の全身臓器における異常プリオン蛋白検出と意義.
2013年度~2015年度, 基盤研究(C), 代表, 病型分類別にみたプリオン蛋白の重合度解析と蛋白化学的異常化の評価.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。
 
 
九州大学知的財産本部「九州大学Seeds集」